Imidazopyridazinone and imidazopyridone derivatives, the preparation thereof and their use as  pharmaceutical compositions

ABSTRACT

The present invention relates to substituted imidazo-pyridinones and imidazo-pyridazinones of general formula 
     
       
         
         
             
             
         
       
     
     wherein Y and R 1  to R 4  are defined as in claim  1 , the tautomers, enantiomers, diastereomers, the mixtures thereof and the salts thereof, which have valuable pharmacological properties, particularly an inhibiting effect on the activity of the enzyme dipeptidylpeptidase-IV (DPP-IV).

RELATED APPLICATIONS

This application claims benefit of U.S. Serial No. PV 60/487,309, filedJul. 15, 2003, and claims priority to German Application No. DE10327439.1 filed Jun. 18, 2003, each of which is hereby incorporated byreference in its entirety.

The present invention relates to new substituted imidazopyridazinonesand imidazopyridones of general formula

the tautomers, the enantiomers, the diastereomers, the mixtures thereof,the prodrugs thereof and the salts thereof, particularly thephysiologically acceptable salts thereof with inorganic or organic acidsor bases which have valuable pharmacological properties, particularly aninhibiting effect on the activity of the enzyme dipeptidylpeptidase-IV(DPP-IV), the preparation thereof, the use thereof for the prevention ortreatment of diseases or conditions associated with an increased DPP-IVactivity or capable of being prevented or alleviated by reducing theDPP-IV activity, particularly type I or type II diabetes mellitus, thepharmaceutical compositions containing a compound of general formula (I)or a physiologically acceptable salt thereof as well as processes forthe preparation thereof.

The present invention thus relates to the above compounds of generalformula I which have valuable pharmacological properties, thepharmaceutical compositions containing the pharmacologically effectivecompounds, the use thereof and processes for the preparation thereof.

In the above general formula I

R¹ denotes a C₁₋₃-alkyl group substituted by a group R_(a), where

-   -   R_(a) denotes a 3,4-dihydro-quinolinyl,        3,4-dihydro-isoquinolinyl, 1,4-dihydro-quinazolinyl,        3,4-dihydro-quinazolinyl, 1H-benzo[d][1,2]oxazinyl,        4H-benzo[e][1,3]-oxazinyl, 4H-benzo[d][1,3]oxazinyl or        2H-benzo[1,4]oxazinyl group, wherein in each case        -   in the benzo moiety one to three methyne groups may each be            replaced by a nitrogen atom and in the heterocyclyl moiety a            methylene group may be replaced by a carbonyl group,    -   a 4H-benzo[e][1,3]thiazinyl, 4H-benzo[d][1,3]thiazinyl or        2H-benzo[1,4]thiazinyl group wherein in each case        -   in the benzo moiety one to three methyne groups may each be            replaced by a nitrogen atom and in the heterocyclyl moiety a            methylene group may be replaced by a carbonyl group and the            sulphur atom may be replaced by a sulphinyl or sulphonyl            group,    -   a 2-oxo-2H-benzo[e][1,3]oxazinyl or        2,2-dioxo-1H-benzo[c][1,2]thiazinyl group wherein in each case        in the benzo moiety        -   one to three methyne groups may each be replaced by a            nitrogen atom,    -   a 2,3-dihydro-1H-benzo[e][1,4]diazepinyl,        4,5-dihydro-3H-benzo[b][1,4]diazepinyl or        5-oxo-4,5-dihydro-3H-benzo[e][1,4]diazepinyl group wherein in        each case        -   in the benzo moiety one to three methyne groups may each be            replaced by a nitrogen atom and in the heterocyclyl moiety a            methylene group may be replaced by a carbonyl group,    -   a 2,3-dihydro-benzo[f][1,4]oxazepinyl or        2,3-dihydro-benzo[b][1,4]oxazepinyl group wherein in each case        -   in the benzo moiety one to three methyne groups may each be            replaced by a nitrogen atom and in the heterocyclyl moiety a            methylene group may be replaced by a carbonyl group,    -   a 2,3-dihydro-benzo[b][1,4]thiazepinyl or        2,3-dihydro-benzo[f][1,4]thiazepinyl group wherein in each case        -   in the benzo moiety one to three methyne groups may each be            replaced by a nitrogen atom and in the heterocyclyl moiety a            methylene group may be replaced by a carbonyl group and the            sulphur atom may be replaced by a sulphinyl or sulphonyl            group,    -   a 5-oxo-4,5-dihydro-benzo[f][1,3,4]oxadiazepinyl group wherein        -   in the benzo moiety one to three methyne groups may each be            replaced by a nitrogen atom,    -   a 11H-dibenzo[b,e]azepinyl or 5H-dibenzo[a,d]cycloheptenyl group        wherein in each case        -   in the benzo moiety one to three methyne groups may each be            replaced by a nitrogen atom and the methylene group in the            heterocyclyl moiety may be replaced by an oxygen or sulphur            atom, a carbonyl, sulphinyl or sulphonyl group or by an            imino group substituted by R_(x), where            -   R_(x) denotes a hydrogen atom or a C₁₋₄-alkyl,                C₂₋₄-alkenyl, C₂₋₄-alkynyl, C₃₋₆-cycloalkyl,                C₃₋₆-cycloalkyl-C₁₋₃-alkyl, aryl, aryl-C₁₋₃-alkyl,                hydroxy-C₂₋₄-alkyl, C₁₋₃-alkyloxy-C₂₋₄-alkyl,                C₃₋₆-cycloalkyloxy-C₂₋₄-alkyl, amino-C₂₋₄-alkyl,                C₁₋₃-alkylamino-C₂₋₄-alkyl,                di-(C₁₋₃-alkyl)-amino-C₂₋₄-alkyl, C₁₋₃-alkyl-carbonyl,                C₁₋₃-alkyloxy-carbonyl,                C₁₋₃-alkyloxy-carbonyl-C₁₋₃-alkyl, aryl-carbonyl,                C₁₋₃-alkyl-sulphonyl or aryl-sulphonyl group,    -   a phenanthridinyl group wherein        -   in the benzo moiety one to three methyne groups may each be            replaced by a nitrogen atom, and    -   a 1,2,3,4-tetrahydro-phenanthridinyl,        1,2,3,4,4a,10b-hexahydro-phenanthridinyl,        2,3-dihydro-1H-4-aza-cyclopenta[a]naphthyl or a        8,9,10,11-tetrahydro-7H-6-aza-cyclohepta[a]naphthyl group        wherein in each case        -   in the benzo moiety one to three methyne groups may each be            replaced by a nitrogen atom and one or two methylene groups            may each be replaced by an oxygen atom or a carbonyl group,            while, if two methylene groups are each replaced by an            oxygen atom, the oxygen atoms must be separated from one            another by at least two methylene units,    -   a phenanthrenyl group wherein        -   in each case one to three of the methyne groups in position            1 to 4 and 5 to 8 may each be replaced by a nitrogen atom,    -   a 1,2,3,4-tetrahydro-phenanthrenyl or a        1,2,3,4,5,6,7,8-octahydro-phenanthrenyl group wherein        -   in each case one or two of the methylene groups in position            1 to 4 and 5 to 8 may each be replaced by an oxygen atom or            a carbonyl group, while, if two methylene groups are each            replaced by an oxygen atom, the oxygen atoms must be            separated from one another by at least two methylene units,    -   a 5H-benzo[e]pyrrolo[1,2-a][1,4]diazepinyl,        thieno[3,2-b][1,4]benzoxazepinyl, 5H-dibenzo[d,f][1,3]diazepinyl        or a 5-oxa-7-aza-dibenzo[a,c]cycloheptenyl group wherein in each        case    -   in the benzo moiety one to three methyne groups may each be        replaced by a nitrogen atom,    -   a naphtho[1,2-d]oxazolyl, naphtho[2,1-d]oxazolyl,        naphtho[1,2-d]thiazolyl, naphtho[2,1-d]thiazolyl,        naphtho[1,2-d]imidazolyl, naphtho[1,2-b]furanyl or        naphtho[2,1-b]furanyl group wherein in each case        -   in the naphthyl moiety one to three methyne groups may each            be replaced by a nitrogen atom,    -   or a furo[3,2-c]isoquinolinyl, pyrazolo[1,5-c]quinazolinyl or        1H-perimidinyl group,    -   while the methylene and methyne groups of the above mentioned        radicals R_(a) may be substituted by the groups R¹⁰ to R¹³ and        additionally by a C₁₋₃-alkyl group and the imino groups of the        above mentioned radicals R_(a) may be substituted by the groups        R_(x) as hereinbefore defined and        -   R¹⁰ denotes a hydrogen atom,        -   a fluorine, chlorine, bromine or iodine atom,        -   a C₁₋₄-alkyl, hydroxy, or C₁₋₄-alkyloxy group,        -   a nitro, amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)amino,            cyano-C₁₋₃-alkylamino,            N-(cyano-C₁₋₃-alkyl)-N—(C₁₋₃-alkyl)-amino,            C₁₋₃-alkyloxy-carbonyl-C₁₋₃-alkylamino, pyrrolidin-1-yl,            piperidin-1-yl, morpholin-4-yl, piperazin-1-yl, or            4-(C₁₋₃-alkyl)-piperazin-1-yl group,        -   a C₁₋₃-alkyl-carbonylamino, arylcarbonylamino,            aryl-C₁₋₃-alkyl-carbonylamino, C₁₋₃-alkyloxy-carbonylamino,            aminocarbonylamino, C₁₋₃-alkylaminocarbonylamino,            di-(C₁₋₃-alkyl)aminocarbonylamino,            pyrrolidin-1-yl-carbonylamino, piperidin-1-yl-carbonylamino,            morpholin-4-yl-carbonylamino, piperazin-1-yl-carbonylamino            or 4-(C₁₋₃-alkyl)-piperazin-1-yl-carbonylamino,            C₁₋₃-alkyl-sulphonylamino, bis-(C₁₋₃-alkylsulphonyl)-amino,            aminosulphonylamino, C₁₋₃-alkylamino-sulphonylamino,            di-(C₁₋₃-alkyl)amino-sulphonylamino,            pyrrolidin-1-yl-sulphonylamino,            piperidin-1-yl-sulphonylamino,            morpholin-4-yl-sulphonylamino, piperazin-1-yl-sulphonylamino            or 4-(C₁₋₃-alkyl)-piperazin-1-yl-sulphonylamino,            (C₁₋₃-alkylamino)thiocarbonylamino,            (C₁₋₃-alkyloxy-carbonylamino)carbonylamino,            arylsulphonylamino or aryl-C₁₋₃-alkyl-sulphonylamino group,        -   an N—(C₁₋₃-alkyl)-C₁₋₃-alkyl-carbonylamino,            N—(C₁₋₃-alkyl)-arylcarbonylamino,            N—(C₁₋₃-alkyl)-aryl-C₁₋₃-alkyl-carbonylamino,            N—(C₁₋₃-alkyl)-C₁₋₃-alkyloxy-carbonylamino,            N-(aminocarbonyl)-C₁₋₃-alkylamino,            N—(C₁₋₃-alkyl-aminocarbonyl)-C₁₋₃-alkylamino,            N—[di-(C₁₋₃-alkyl)aminocarbonyl]-C₁₋₃-alkylamino,            N—(C₁₋₃-alkyl)-C₁₋₃-alkyl-sulphonylamino,            N—(C₁₋₃-alkyl)-arylsulphonylamino, or            N—(C₁₋₃-alkyl)-aryl-C₁₋₃-alkyl-sulphonylamino group,        -   a 2-oxo-imidazolidin-1-yl, 2,4-dioxo-imidazolidin-1-yl,            2,5-dioxo-imidazolidin-1-yl or 2-oxo-hexahydropyrimidin-1-yl            group wherein the nitrogen atom in the 3 position may be            substituted in each case by a methyl or ethyl group,        -   a cyano, carboxy, C₁₋₃-alkyloxy-carbonyl, aminocarbonyl,            C₁₋₃-alkyl-aminocarbonyl, di-(C₁₋₃-alkyl)-aminocarbonyl,            pyrrolidin-1-yl-carbonyl, piperidin-1-yl-carbonyl,            morpholin-4-yl-carbonyl, piperazin-1-yl-carbonyl or            4-(C₁₋₃-alkyl)-piperazin-1-yl-carbonyl group,        -   a C₁₋₃-alkyl-carbonyl or an arylcarbonyl group,        -   a carboxy-C₁₋₃-alkyl, C₁₋₃-alkyloxy-carbonyl-C₁₋₃-alkyl,            cyano-C₁₋₃-alkyl, aminocarbonyl-C₁₋₃-alkyl,            C₁₋₃-alkyl-aminocarbonyl-C₁₋₃-alkyl,            di-(C₁₋₃-alkyl)-aminocarbonyl-C₁₋₃-alkyl,            pyrrolidin-1-yl-carbonyl-C₁₋₃-alkyl,            piperidin-1-yl-carbonyl-C₁₋₃-alkyl,            morpholin-4-yl-carbonyl-C₁₋₃-alkyl,            piperazin-1-yl-carbonyl-C₁₋₃-alkyl or            4-(C₁₋₃-alkyl)-piperazin-1-yl-carbonyl-C₁₋₃-alkyl group,        -   a carboxy-C₁₋₃-alkyloxy,            C₁₋₃-alkyloxy-carbonyl-C₁₋₃-alkyloxy, cyano-C₁₋₃-alkyloxy,            aminocarbonyl-C₁₋₃-alkyloxy,            C₁₋₃-alkyl-aminocarbonyl-C₁₋₃-alkyloxy,            di-(C₁₋₃-alkyl)-aminocarbonyl-C₁₋₃-alkyloxy,            pyrrolidin-1-yl-carbonyl-C₁₋₃-alkyloxy,            piperidin-1-yl-carbonyl-C₁₋₃-alkyloxy,            morpholin-4-yl-carbonyl-C₁₋₃-alkyloxy,            piperazin-1-yl-carbonyl-C₁₋₃-alkyloxy or            4-(C₁₋₃-alkyl)-piperazin-1-yl-carbonyl-C₁₋₃-alkyloxy group,        -   a hydroxy-C₁₋₃-alkyl, C₁₋₃-alkyloxy-C₁₋₃-alkyl,            amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl,            di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl,            pyrrolidin-1-yl-C₁₋₃-alkyl, piperidin-1-yl-C₁₋₃-alkyl,            morpholin-4-yl-C₁₋₃-alkyl, piperazin-1-yl-C₁₋₃-alkyl or            4-(C₁₋₃-alkyl)-piperazin-1-yl-C₁₋₃-alkyl group,        -   a hydroxy-C₁₋₃-alkyloxy, C₁₋₃-alkyloxy-C₁₋₃-alkyloxy,            C₁₋₃-alkylsulphanyl-C₁₋₃-alkyloxy,            C₁₋₃-alkylsulphinyl-C₁₋₃-alkyloxy,            C₁₋₃-alkylsulphonyl-C₁₋₃-alkyloxy, amino-C₁₋₃-alkyloxy,            C₁₋₃-alkylamino-C₁₋₃-alkyloxy,            di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyloxy,            pyrrolidin-1-yl-C₁₋₃-alkyloxy, piperidin-1-yl-C₁₋₃-alkyloxy,            morpholin-4-yl-C₁₋₃-alkyloxy, piperazin-1-yl-C₁₋₃-alkyloxy            or 4-(C₁₋₃-alkyl)-piperazin-1-yl-C₁₋₃-alkyloxy group,        -   a mercapto, C₁₋₃-alkylsulphanyl, C₁₋₃-alkysulphinyl,            C₁₋₃-alkylsulphonyl, C₁₋₃-alkylsulphonyloxy,            arylsulphonyloxy, trifluoromethylsulphanyl,            trifluoromethylsulphinyl or trifluoromethylsulphonyl group,        -   a sulpho, aminosulphonyl, C₁₋₃-alkyl-aminosulphonyl,            di-(C₁₋₃-alkyl)-aminosulphonyl, pyrrolidin-1-yl-sulphonyl,            piperidin-1-yl-sulphonyl, morpholin-4-yl-sulphonyl,            piperazin-1-yl-sulphonyl or            4-(C₁₋₃-alkyl)-piperazin-1-yl-sulphonyl group,        -   a methyl or methoxy group substituted by 1 to 3 fluorine            atoms,        -   an ethyl or ethoxy group substituted by 1 to 5 fluorine            atoms,        -   a C₂₋₄-alkenyl or C₂₋₄-alkynyl group,        -   a C₃₋₄-alkenyloxy or C₃₋₄-alkynyloxy group,        -   a C₃₋₆-cycloalkyl or C₃₋₆-Cycloalkyloxy group,        -   a C₃₋₆-cycloalkyl-C₁₋₃-alkyl or            C₃₋₆-cycloalkyl-C₁₋₃-alkyloxy group or        -   an aryl, aryloxy, aryl-C₁₋₃-alkyl or aryl-C₁₋₃-alkyloxy            group,        -   R¹¹ and R¹², which may be identical or different, in each            case represent a hydrogen atom, a fluorine, chlorine,            bromine or iodine atom, a C₁₋₃-alkyl, trifluoromethyl,            hydroxy, C₁₋₃-alkyloxy or cyano group, or        -   R¹¹ together with R¹², if these are bound to adjacent carbon            atoms, also denotes a methylenedioxy,            difluoromethylenedioxy, ethylenedioxy or a straight-chain            C₃₋₅-alkylene group and        -   R¹³ denotes a hydrogen atom, a fluorine, chlorine or bromine            atom, a trifluoromethyl, C₁₋₃-alkyl or C₁₋₃-alkyloxy group,            R² denotes a hydrogen, fluorine or chlorine atom,            a C₁₋₆-alkyl group,            a C₂₋₄-alkenyl group,            a C₃₋₄-alkynyl group,            a C₃₋₆-cycloalkyl group,            a C₃₋₆-cycloalkyl-C₁₋₃-alkyl group,            a tetrahydrofuran-3-yl, tetrahydropyran-3-yl,            tetrahydropyran-4-yl, tetrahydrofuranylmethyl or            tetrahydropyranylmethyl group,            an aryl group,            an aryl-C₁₋₄-alkyl group,            an aryl-C₂₋₃-alkenyl group,            an arylcarbonyl group,            an arylcarbonyl-C₁₋₂-alkyl group,            a heteroaryl group,            a heteroaryl-C₁₋₃-alkyl group,            a furanylcarbonyl, thienylcarbonyl, thiazolylcarbonyl or            pyridylcarbonyl group,            a furanylcarbonylmethyl, thienylcarbonylmethyl,            thiazolylcarbonylmethyl or pyridylcarbonylmethyl group,            a C₁₋₄-alkyl-carbonyl group,            a C₁₋₄-alkyl-carbonyl-C₁₋₂-alkyl group,            a C₃₋₆-cycloalkyl-carbonyl group,            a C₃₋₆-cycloalkyl-carbonyl-C₁₋₂-alkyl group,            an aryl-A or aryl-A-C₁₋₃-alkyl group, where A denotes an            oxygen or sulphur atom, an imino, C₁₋₃-alkylimino, sulphinyl            or sulphonyl group,            a group R_(b), where    -   R_(b) denotes a cyano, carboxy, C₁₋₃-alkyloxy-carbonyl,        aminocarbonyl, C₁₋₃-alkylamino-carbonyl,        di-(C₁₋₃-alkyl)-amino-carbonyl, pyrrolidin-1-ylcarbonyl,        piperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl,        piperazin-1-ylcarbonyl, 4-methylpiperazin-1-ylcarbonyl,        4-ethylpiperazin-1-ylcarbonyl, hydroxy, mercapto, C₁₋₃-alkyloxy,        C₁₋₃-alkylsulphenyl, C₁₋₃-alkylsulphinyl, C₁₋₃-alkylsulphonyl,        amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino, pyrrolidin-1-yl,        piperidin-1-yl, morpholin-4-yl, piperazin-1-yl,        4-methyl-piperazin-1-yl or 4-ethyl-piperazin-1-yl group,        or a C₁₋₄-alkyl group substituted by a group R_(b), where R_(b)        is as hereinbefore defined,        Y denotes a nitrogen atom or a group of formula C—R⁵,    -   while R⁵ is defined like R² and in each case one of the two        groups R² and R⁵ must be a hydrogen atom or a C₁₋₃-alkyl group,        R³ denotes a C₃₋₈-alkyl group,        a C₁₋₃-alkyl group substituted by a group R_(c), where    -   R_(c), denotes a C₃₋₇-cycloalkyl group optionally substituted by        one or two C₁₋₃-alkyl groups,    -   a C₅₋₇-cycloalkenyl group optionally substituted by one or two        C₁₋₃-alkyl groups,    -   an aryl group or    -   a furanyl, thienyl, oxazolyl, isoxazolyl, thiazolyl,        isothiazolyl, pyridyl, pyridazinyl, pyrimidyl or pyrazinyl        group, while the above mentioned heterocyclic groups may each be        substituted by one or two C₁₋₃-alkyl groups or by a fluorine,        chlorine, bromine or iodine atom or by a trifluoromethyl, cyano        or C₁₋₃-alkyloxy group,        a C₃₋₈-alkenyl group,        a C₃₋₆-alkenyl group substituted by a fluorine, chlorine or        bromine atom or by a trifluoromethyl group,        a C₃₋₈-alkynyl group,        an aryl group or        an aryl-C₂₋₄-alkenyl group,        and        R⁴ denotes an azetidin-1-yl or pyrrolidin-1-yl group which is        substituted in the 3 position by an amino, C₁₋₃-alkylamino or a        di-(C₁₋₃-alkyl)amino group and may additionally be substituted        by one or two C₁₋₃-alkyl groups,        a piperidin-1-yl or hexahydroazepin-1-yl group which is        substituted in the 3 position or in the 4 position by an amino,        C₁₋₃-alkylamino or a di-(C₁₋₃-alkyl)amino group and may        additionally be substituted by one or two C₁₋₃-alkyl groups,        a 3-amino-piperidin-1-yl group wherein the piperidin-1-yl moiety        is additionally substituted by an aminocarbonyl,        C₁₋₂-alkyl-aminocarbonyl, di-(C₁₋₂-alkyl)aminocarbonyl,        pyrrolidin-1-yl-carbonyl, (2-cyano-pyrrolidin-1-yl-)carbonyl,        thiazolidin-3-yl-carbonyl, (4-cyano-thiazolidin-3-yl)carbonyl,        piperidin-1-ylcarbonyl or morpholin-4-ylcarbonyl group,        a 3-amino-piperidin-1-yl group wherein the piperidin-1-yl moiety        in the 4 position or in the 5 position is additionally        substituted by a hydroxy or methoxy group,        a 3-amino-piperidin-1-yl group wherein the methylene group in        the 2 position or in the 6 position is replaced by a carbonyl        group,        a piperidin-1-yl or hexahydroazepin-1-yl group substituted in        the 3 position by an amino, C₁₋₃-alkylamino or        di-(C₁₋₃-alkyl)-amino-group, wherein in each case two hydrogen        atoms on the carbon skeleton of the piperidin-1-yl or        hexahydroazepin-1-yl-group are replaced by a straight-chain        alkylene bridge, this bridge containing 2 to 5 carbon atoms if        the two hydrogen atoms are located on the same carbon atom, or 1        to 4 carbon atoms, if the hydrogen atoms are located on adjacent        carbon atoms, or 1 to 4 carbon atoms, if the hydrogen atoms are        located on carbon atoms which are separated by one atom, or 1 to        3 carbon atoms if the two hydrogen atoms are located on carbon        atoms separated by two atoms,        an azetidin-1-yl, pyrrolidin-1-yl, piperidin-1-yl or        hexahydroazepin-1-yl group which is substituted by an        amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl or a        di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl group,        a piperazin-1-yl or [1,4]diazepan-1-yl group optionally        substituted at the carbon skeleton by one or two C₁₋₃-alkyl        groups,        a 3-imino-piperazin-1-yl, 3-imino-[1,4]diazepan-1-yl or        5-imino-[1,4]diazepan-1-yl group optionally substituted at the        carbon skeleton by one or two C₁₋₃-alkyl groups,        a [1,4]diazepan-1-yl group optionally substituted by one or two        C₁₋₃-alkyl groups, which is substituted in the 6 position by an        amino group,        a C₃₋₇-cycloalkyl group which is substituted by an amino,        C₁₋₃-alkylamino or di-(C₁₋₃-alkyl)-amino group,        a C₃₋₇-cycloalkyl group which is substituted by an        amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl or a        di-(C₁₋₃-alkyl)amino-C₁₋₃-alkyl group,        a C₃₋₇-cycloalkyl-C₁₋₂-alkyl group wherein the cycloalkyl moiety        is substituted by an amino, C₁₋₃-alkylamino or        di-(C₁₋₃-alkyl)-amino group,        a C₃₋₇-cycloalkyl-C₁₋₂-alkyl group wherein the cycloalkyl moiety        is substituted by an amino-C₁₋₃-alkyl,        C₁₋₃-alkylamino-C₁₋₃-alkyl or a di-(C₁₋₃-alkyl)amino-C₁₋₃-alkyl        group,        a C₃₋₇-cycloalkylamino group wherein the cycloalkyl moiety is        substituted by an amino, C₁₋₃-alkylamino or        di-(C₁₋₃-alkyl)-amino group, while the two nitrogen atoms at the        cycloalkyl moiety are separated from one another by at least two        carbon atoms,        an N—(C₃₋₇-cycloalkyl)-N—(C₁₋₃-alkyl)-amino group wherein the        cycloalkyl moiety is substituted by an amino, C₁₋₃-alkylamino or        di-(C₁₋₃-alkyl)-amino group, while the two nitrogen atoms at the        cycloalkyl moiety are separated from one another by at least two        carbon atoms,        a C₃₋₇-cycloalkylamino group wherein the cycloalkyl moiety is        substituted by an amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl        or a di-(C₁₋₃-alkyl)amino-C₁₋₃-alkyl group,        an N—(C₃₋₇-cycloalkyl)-N—(C₁₋₃-alkyl)-amino group wherein the        cycloalkyl moiety is substituted by an amino-C₁₋₃-alkyl,        C₁₋₃-alkylamino-C₁₋₃-alkyl or a di-(C₁₋₃-alkyl)amino-C₁₋₃-alkyl        group,        a C₃₋₇-cycloalkyl-C₁₋₂-alkyl-amino group wherein the cycloalkyl        moiety is substituted by an amino, C₁₋₃-alkylamino or        di-(C₁₋₃-alkyl)-amino group,        an N—(C₃₋₇-cycloalkyl-C₁₋₂-alkyl)-N—(C₁₋₂-alkyl)-amino group        wherein the cycloalkyl moiety is substituted by an amino,        C₁₋₃-alkylamino or di-(C₁₋₃-alkyl)-amino group,        a C₃₋₇-cycloalkyl-C₁₋₂-alkyl-amino group wherein the cycloalkyl        moiety is substituted by an amino-C₁₋₃-alkyl,        C₁₋₃-alkylamino-C₁₋₃-alkyl or a di-(C₁₋₃-alkyl)amino-C₁₋₃-alkyl        group,        an N—(C₃₋₇-cycloalkyl-C₁₋₂-alkyl)-N—(C₁₋₂-alkyl)-amino group        wherein the cycloalkyl moiety is substituted by an        amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl or a        di-(C₁₋₃-alkyl)amino-C₁₋₃-alkyl group,        a R¹⁹—C₂₋₄-alkylamino group wherein R¹⁹ is separated from the        nitrogen atom of the C₂₋₄-alkylamino moiety by at least two        carbon atoms and    -   R¹⁹ denotes an amino, C₁₋₃-alkylamino or di-(C₁₋₃-alkyl)-amino        group,        an R¹⁹—C₂₋₄-alkylamino group wherein the nitrogen atom of the        C₂₋₄-alkylamino moiety is substituted by a C₁₋₃-alkyl group and        R¹⁹ is separated from the nitrogen atom of the C₂₋₄-alkylamino        moiety by at least two carbon atoms, while R¹⁹ is as        hereinbefore defined,        an amino group substituted by the group R²⁰ wherein    -   R²⁰ denotes an azetidin-3-yl, azetidin-2-ylmethyl,        azetidin-3-ylmethyl, pyrrolidin-3-yl, pyrrolidin-2-ylmethyl,        pyrrolidin-3-ylmethyl, piperidin-3-yl, piperidin-4-yl,        piperidin-2-ylmethyl, piperidin-3-ylmethyl or        piperidin-4-ylmethyl group, while the groups mentioned for R²⁰        may each be substituted by one or two C₁₋₃-alkyl groups,        an amino group substituted by the group R²⁰ and a C₁₋₃-alkyl        group wherein R²⁰ is as hereinbefore defined, while the groups        mentioned for R²⁰ may each be substituted by one or two        C₁₋₃-alkyl groups,        an R¹⁹—C₃₋₄-alkyl group wherein the C₃₋₄-alkyl moiety is        straight-chained and may additionally be substituted by one or        two C₁₋₃-alkyl groups, while R¹⁹ is as hereinbefore defined,        a 3-amino-2-oxo-piperidin-5-yl or        3-amino-2-oxo-1-methyl-piperidin-5-yl group,        a pyrrolidin-3-yl, piperidin-3-yl, piperidin-4-yl,        hexahydroazepin-3-yl or hexahydroazepin-4-yl group which is        substituted in the 1 position by an amino, C₁₋₃-alkylamino or        di-(C₁₋₃-alkyl)amino group,        or an azetidin-2-yl-C₁₋₂-alkyl, azetidin-3-yl-C₁₋₂-alkyl,        pyrrolidin-2-yl-C₁₋₂-alkyl, pyrrolidin-3-yl,        pyrrolidin-3-yl-C₁₋₂-alkyl, piperidin-2-yl-C₁₋₂-alkyl,        piperidin-3-yl, piperidin-3-yl-C₁₋₂-alkyl, piperidin-4-yl or        piperidin-4-yl-C₁₋₂-alkyl group, while the above mentioned        groups may each be substituted by one or two C₁₋₃-alkyl groups,        while by the aryl groups mentioned in the definition of the        above groups are meant phenyl or naphthyl groups which may be        mono- or disubstituted by R_(h), while the substituents may be        identical or different and R_(h) denotes a fluorine, chlorine,        bromine or iodine atom, a trifluoromethyl, cyano, nitro, amino,        aminocarbonyl, aminosulphonyl, methylsulphonyl, acetylamino,        methylsulphonylamino, C₁₋₃-alkyl, cyclopropyl, ethenyl, ethynyl,        hydroxy, C₁₋₃-alkyloxy, difluoromethoxy or trifluoromethoxy        group,        by the heteroaryl groups mentioned in the definition of the        above groups are meant a pyrrolyl, furanyl, thienyl, pyridyl,        indolyl, benzofuranyl, benzothiophenyl, quinolinyl or        isoquinolinyl group,        or a pyrrolyl, furanyl, thienyl or pyridyl group, wherein one or        two methyne groups are replaced by nitrogen atoms,        or an indolyl, benzofuranyl, benzothiophenyl, quinolinyl or        isoquinolinyl group, wherein one to three methyne groups are        replaced by nitrogen atoms,    -   and the above mentioned heteroaryl groups may be mono- or        disubstituted by R_(h), while the substituents may be identical        or different and R_(h) is as hereinbefore defined,        while, unless otherwise stated, the above mentioned alkyl,        alkenyl and alkynyl groups may be straight-chain or branched,        and the hydrogen atoms of the methyl or ethyl groups contained        in the definitions may be wholly or partly replaced by fluorine        atoms,        the tautomers, enantiomers, diastereomers, the mixtures thereof,        the prodrugs thereof and the salts thereof.

Compounds of the above general formula I which contain one or moregroups that can be cleaved in vivo are so-called prodrugs.

The carboxy groups mentioned in the definition of the above mentionedgroups may be replaced by a group which can be converted into a carboxygroup in vivo or by a group which is negatively charged underphysiological conditions,

and furthermore the amino and imino groups mentioned in the definitionof the above mentioned groups may be substituted by a group which can becleaved in vivo. Such groups are described for example in WO 98/46576and by N. M. Nielsen et al. in International Journal of Pharmaceutics39, 75-85 (1987).

By a group which can be converted in vivo into a carboxy group is meant,for example, a hydroxymethyl group, a carboxy group esterified with analcohol wherein the alcohol moiety is preferably a C₁₋₆-alkanol, aphenyl-C₁₋₃-alkanol, a C₃₋₉-cycloalkanol, while a C₅₋₈-cycloalkanol mayadditionally be substituted by one or two C₁₋₃-alkyl groups, aC₅₋₈-cycloalkanol wherein a methylene group in the 3 or 4 position isreplaced by an oxygen atom or by an imino group optionally substitutedby a C₁₋₃-alkyl, phenyl-C₁₋₃-alkyl, phenyl-C₁₋₃-alkyloxycarbonyl orC₂₋₆-alkanoyl group and the cycloalkanol moiety may additionally besubstituted by one or two C₁₋₃-alkyl groups, a C₄₋₇-cycloalkenol, aC₃₋₅-alkenol, a phenyl-C₃₋₅-alkenol, a C₃₋₅-alkynol orphenyl-C₃₋₅-alkynol with the proviso that no bonds to the oxygen atomstart from a carbon atom which carries a double or triple bond, aC₃₋₈-cycloalkyl-C₁₋₃-alkanol, a bicycloalkanol with a total of 8 to 10carbon atoms which may additionally be substituted in the bicycloalkylmoiety by one or two C₁₋₃-alkyl groups, a1,3-dihydro-3-oxo-1-isobenzofuranol or an alcohol of formula

R_(p)—CO—O—(R_(q)CR_(r))—OH,

wherein

-   -   R_(p) denotes a C₁₋₈-alkyl, C₅₋₇-cycloalkyl, C₁₋₈-alkyloxy,        C₅₋₇-cycloalkyloxy, phenyl or phenyl-C₁₋₃-alkyl group,    -   R_(q) denotes a hydrogen atom, a C₁₋₃-alkyl, C₅₋₇-cycloalkyl or        phenyl group and    -   R_(r) denotes a hydrogen atom or a C₁₋₃-alkyl group,        by a group which is negatively charged under physiological        conditions is meant, for example, a tetrazol-5-yl,        phenylcarbonylaminocarbonyl,        trifluoromethylcarbonylaminocarbonyl, C₁₋₆-alkylsulphonylamino,        phenylsulphonylamino, benzylsulphonylamino,        trifluoromethyl-sulphonylamino,        C₁₋₆-alkylsulphonylaminocarbonyl, phenylsulphonylaminocarbonyl,        benzylsulphonylaminocarbonyl or        perfluoro-C₁₋₆-alkylsulphonylaminocarbonyl group        and by a group which can be cleaved in vivo from an imino or        amino group is meant, for example, a hydroxy group, an acyl        group such as a phenylcarbonyl group optionally mono- or        disubstituted by fluorine, chlorine, bromine or iodine atoms, by        C₁₋₃-alkyl or C₁₋₃-alkyloxy groups, while the substituents may        be identical or different, a pyridinoyl group or a        C₁₋₁₆-alkanoyl group such as the formyl, acetyl, propionyl,        butanoyl, pentanoyl or hexanoyl group, a        3,3,3-trichloropropionyl or allyloxycarbonyl group, a        C₁₋₁₆-alkyloxycarbonyl or C₁₋₆-alkylcarbonyloxy group, wherein        hydrogen atoms may be wholly or partially replaced by fluorine        or chlorine atoms such as the methoxycarbonyl, ethoxycarbonyl,        propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl,        tert.butoxycarbonyl, pentoxycarbonyl, hexoxycarbonyl,        octyloxycarbonyl, nonyloxycarbonyl, decyloxycarbonyl,        undecyloxycarbonyl, dodecyloxycarbonyl, hexadecyloxycarbonyl,        methylcarbonyloxy, ethylcarbonyloxy,        2,2,2-trichloroethylcarbonyloxy, propylcarbonyloxy,        isopropylcarbonyloxy, butylcarbonyloxy, tert.butylcarbonyloxy,        pentylcarbonyloxy, hexylcarbonyloxy, octylcarbonyloxy,        nonylcarbonyloxy, decylcarbonyloxy, undecylcarbonyloxy,        dodecylcarbonyloxy or hexadecylcarbonyloxy group, a        phenyl-C₁₋₆-alkyloxycarbonyl group such as the        benzyloxycarbonyl, phenylethoxycarbonyl or phenylpropoxycarbonyl        group, a 3-amino-propionyl group wherein the amino group may be        mono- or disubstituted by C₁₋₆-alkyl or C₃₋₇-cycloalkyl groups        and the substituents may be identical or different, a        C₁₋₃-alkylsulphonyl-C₂₋₄-alkyloxycarbonyl,        C₁₋₃-alkyloxy-C₂₋₄-alkyloxy-C₂₋₄-alkyloxycarbonyl,        R_(p)—CO—O—(R_(q)CR_(r))—O—CO,        C₁₋₆-alkyl-CO—NH—(R_(s)CR_(t))—O—CO or        C₁₋₆-alkyl-CO—O—(R_(s)CR_(t))—(R_(s)CR_(t))—O—CO group, wherein        R_(p) to R_(r) are as hereinbefore defined,    -   R_(s), and R_(t), which may be identical or different, denote        hydrogen atoms or C₁₋₃-alkyl groups.

Moreover, the saturated alkyl and alkyloxy moieties which contain morethan 2 carbon atoms mentioned in the foregoing definitions and thosethat follow, unless otherwise stated, also include the branched isomersthereof such as, for example, the isopropyl, tert.butyl, isobutyl group,etc.

Preferred compounds of the above general formula I are those wherein

R¹ denotes a methyl group substituted by a group R_(a), where

-   -   R_(a) denotes a 3,4-dihydro-quinolinyl group,    -   a 3,4-dihydro-isoquinolinyl group,    -   a 1,4-dihydro-quinazolinyl or 4-oxo-1,4-dihydro-quinazolinyl        group,    -   a 3,4-dihydro-quinazolinyl or 4-oxo-3,4-dihydro-quinazolinyl        group,    -   a 1H-benzo[d][1,2]oxazinyl or 1-oxo-1H-benzo[d][1,2]oxazinyl        group,    -   a 4H-benzo[e][1,3]oxazinyl or 4-oxo-4H-benzo[e][1,3]oxazinyl        group,    -   a 4H-benzo[d][1,3]oxazinyl or 4-oxo-4H-benzo[d][1,3]oxazinyl        group,    -   a 2H-benzo[1,4]oxazinyl or 2-oxo-2H-benzo[1,4]oxazinyl group,    -   a 4H-benzo[e][1,3]thiazinyl or 4-oxo-4H-benzo[e][1,3]thiazinyl        group,    -   a 4H-benzo[d][1,3]thiazinyl or 2H-benzo[1,4]thiazinyl group,    -   a 2-oxo-2H-benzo[e][1,3]oxazinyl or        2,2-dioxo-1H-benzo[c][1,2]thiazinyl group,    -   a 2,3-dihydro-1H-benzo[e][1,4]diazepinyl or        2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepinyl group,    -   a 4,5-dihydro-3H-benzo[b][1,4]diazepinyl or        4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepinyl group,    -   a 5-oxo-4,5-dihydro-3H-benzo[e][1,4]diazepinyl group,    -   a 2,3-dihydro-benzo[f][1,4]oxazepinyl or        2,3-dihydro-benzo[b][1,4]oxazepinyl group,    -   a 2,3-dihydro-benzo[f][1,4]thiazepinyl or        2,3-dihydro-benzo[b][1,4]thiazepinyl group,    -   a 5-oxo-4,5-dihydro-benzo[f][1,3,4]oxadiazepinyl group,    -   a 11H-dibenzo[b,e]azepinyl or 11-oxo-11H-dibenzo[b,e]azepinyl        group,    -   a 11H-benzo[e]pyrido[3,2-b]azepinyl or a        5H-1,9,10-triaza-dibenzo[a,d]cycloheptenyl group,    -   a 5H-dibenzo[b,e][1,4]diazepinyl or dibenzo[b,f][1,4]oxazepinyl        group,    -   a dibenzo[b,f][1,4]thiazepinyl,        5-oxo-dibenzo[b,f][1,4]thiazepinyl or        5,5-dioxo-dibenzo[b,f][1,4]thiazepinyl group,    -   a 5H-dibenzo[a,d]cycloheptenyl or 5H-dibenzo[b,f]azepinyl group,    -   a phenanthridinyl, benzo[c][1,5]naphthyridinyl,        benzo[h][1,6]naphthyridinyl, benzo[c][1,8]naphthyridinyl,        benzo[f][1,7]naphthyridinyl or 1,5,9-triaza-phenanthrenyl group,    -   a 1,2,3,4-tetrahydro-phenanthridinyl,        1,2,3,4,4a,10b-hexahydro-phenanthridinyl,        2,3-dihydro-1H-4-aza-cyclopenta[a]naphthyl or        8,9,10,11-tetrahydro-7H-6-aza-cyclohepta[a]naphthyl group,    -   a 2,3-dihydro-1H-4-oxa-10-aza-phenanthrenyl or        1-oxo-2,3-dihydro-1H-4-oxa-10-aza-phenanthrenyl group,    -   a phenanthrenyl, benzo[h]quinolinyl, benzo[f]quinolinyl or        benzo[f]quinoxalinyl group,    -   a 5H-benzo[e]pyrrolo[1,2-a][1,4]diazepinyl,        thieno[3,2-b][1,4]benzoxazepinyl, 5H-dibenzo[d,f][1,3]diazepinyl        or 5-oxa-7-aza-dibenzo[a,c]cycloheptenyl group,    -   a naphtho[1,2-d]oxazolyl, naphtho[2,1-d]oxazolyl,        naphtho[1,2-d]thiazolyl, naphtho[2,1-d]thiazolyl,        naphtho[1,2-d]imidazolyl, naphtho[1,2-b]furanyl or        naphtho[2,1-b]furanyl group,    -   or a furo[3,2-c]isoquinolinyl, pyrazolo[1,5-c]quinazolinyl or        1H-perimidinyl group,    -   while the benzo groups of the above mentioned radicals R_(a) are        substituted by the groups R¹⁰ to R¹³ and the alkylene units of        the above mentioned groups R_(a) may be substituted by one or        two fluorine atoms or one or two C₁₋₃-alkyl or        C₁₋₃-alkyloxy-carbonyl groups and the imino groups of the above        mentioned radicals R_(a) may be substituted by a C₁₋₃-alkyl        group and        -   R¹⁰ denotes a hydrogen atom,        -   a fluorine, chlorine, bromine or iodine atom,        -   a C₁₋₃-alkyl or cyclopropyl group,        -   a hydroxy, C₁₋₃-alkyloxy or cyclopropyloxy group,        -   a nitro, amino, C₁₋₃-alkylamino or di-(C₁₋₃-alkyl)amino            group,        -   a C₁₋₃-alkyl-carbonylamino or C₁₋₃-alkyl-sulphonylamino            group,        -   a cyano, carboxy, C₁₋₃-alkyloxy-carbonyl, aminocarbonyl,            C₁₋₃-alkyl-aminocarbonyl or di-(C₁₋₃-alkyl)-aminocarbonyl            group,        -   a mercapto, C₁₋₃-alkylsulphanyl, C₁₋₃-alkysulphinyl,            C₁₋₃-alkylsulphonyl or aminosulphonyl group or        -   a difluoromethyl, trifluoromethyl, difluoromethoxy or            trifluoromethoxy group and        -   R¹¹, R¹² and R¹³, which may be identical or different, in            each case represent a hydrogen atom, a fluorine, chlorine or            bromine atom, a methyl, trifluoromethyl or methoxy group,            R² denotes a hydrogen atom or            a C₁₋₃-alkyl, cyclopropyl, trifluoromethyl, cyanomethyl or            2-cyano-ethyl group,            Y denotes a nitrogen atom or a group of formula C—R⁵,    -   while R⁵ denotes a hydrogen atom or a C₁₋₃-alkyl group,        R³ denotes a 2-buten-1-yl or 3-methyl-2-buten-1-yl group,        a 1-buten-1-yl group,        a 2-butyn-1-yl group or        a 1-cyclopenten-1-ylmethyl group        and        R⁴ denotes a (3-amino-piperidin-1-yl) group,        while, unless otherwise stated, the above mentioned alkyl groups        may be straight-chain or branched,        the tautomers, enantiomers, diastereomers, the mixtures thereof        and the salts thereof.

Particularly preferred are those compounds of the above general formulaI wherein

R¹ denotes a methyl group substituted by a group R_(a), where

-   -   R_(a) denotes a 3,4-dihydro-quinolin-2-yl group,    -   a 3,4-dihydro-isoquinolin-1-yl group,    -   a 1,4-dihydro-quinazolin-2-yl or        4-oxo-1,4-dihydro-quinazolin-2-yl group,    -   a 3,4-dihydro-quinazolin-2-yl or        4-oxo-3,4-dihydro-quinazolin-2-yl group,    -   a 1H-benzo[d][1,2]oxazin-4-yl or        1-oxo-1H-benzo[d][1,2]oxazin-4-yl group,    -   a 4H-benzo[e][1,3]oxazin-2-yl or        4-oxo-4H-benzo[e][1,3]oxazin-2-yl group,    -   a 4H-benzo[d][1,3]oxazin-2-yl or        4-oxo-4H-benzo[d][1,3]oxazin-2-yl group,    -   a 2H-benzo[1,4]oxazin-3-yl or 2-oxo-2H-benzo[1,4]oxazin-3-yl        group,    -   a 4H-benzo[e][1,3]thiazin-2-yl or        4-oxo-4H-benzo[e][1,3]thiazin-2-yl group,    -   a 4H-benzo[d][1,3]thiazin-2-yl or 2H-benzo[1,4]thiazin-3-yl        group,    -   a 2-oxo-2H-benzo[e][1,3]oxazin-4-yl or        2,2-dioxo-1H-benzo[c][1,2]thiazin-4-yl group,    -   a 2,3-dihydro-1H-benzo[e][1,4]diazepin-5-yl or        2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-5-yl group,    -   a 4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl or        4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl group,    -   a 5-oxo-4,5-dihydro-3H-benzo[e][1,4]diazepin-2-yl group,    -   a 2,3-dihydro-benzo[f][1,4]oxazepin-5-yl or        2,3-dihydro-benzo[b][1,4]oxazepin-4-yl group,    -   a 2,3-dihydro-benzo[f][1,4]thiazepin-5-yl or        2,3-dihydro-benzo[b][1,4]thiazepin-4-yl group,    -   a 5-oxo-4,5-dihydro-benzo[f][1,3,4]oxadiazepin-2-yl group,    -   a 11H-dibenzo[b,e]azepin-6-yl or        11-oxo-11H-dibenzo[b,e]azepin-6-yl group,    -   a 11H-benzo[e]pyrido[3,2-b]azepin-6-yl or a        5H-1,9,10-triaza-dibenzo[a,d]-cyclohepten-11-yl group,    -   a 5H-dibenzo[b,e][1,4]diazepin-11-yl or        dibenzo[b,f][1,4]oxazepin-11-yl group,    -   a dibenzo[b,f][1,4]thiazepin-11-yl,        5-oxo-dibenzo[b,f][1,4]thiazepin-11-yl or        5,5-dioxo-dibenzo[b,f][1,4]thiazepin-11-yl group,    -   a 5H-dibenzo[a,d]cyclohepten-10-yl or        5H-dibenzo[b,f]azepin-10-yl group,    -   a phenanthridin-6-yl, benzo[c][1,5]naphthyridin-6-yl,        benzo[h][1,6]naphthyridin-5-yl, benzo[c][1,8]naphthyridin-6-yl,        benzo[f][1,7]naphthyridin-5-yl or 1,5,9-triaza-phenanthren-10-yl        group,    -   a 1,2,3,4-tetrahydro-phenanthridin-6-yl,        1,2,3,4,4a,10b-hexahydro-phenanthridin-6-yl,        2,3-dihydro-1H-4-aza-cyclopenta[a]naphth-5-yl or        8,9,10,11-tetrahydro-7H-6-aza-cyclohepta[a]naphth-5-yl group,    -   a 2,3-dihydro-1H-4-oxa-10-aza-phenanthren-9-yl or        1-oxo-2,3-dihydro-1H-4-oxa-10-aza-phenanthren-9-yl group,    -   a phenanthren-9-yl, benzo[h]quinolin-6-yl, benzo[f]quinolin-6-yl        or benzo[f]quinoxalin-6-yl group,    -   a 5H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-11-yl,        thieno[3,2-b][1,4]benzoxazepin-9-yl,        5H-dibenzo[d,f][1,3]diazepin-6-yl or        5-oxa-7-aza-dibenzo[a,c]cyclohepten-6-yl group,    -   a naphtho[1,2-d]oxazol-2-yl, naphtho[2,1-d]oxazol-2-yl,        naphtho[1,2-d]thiazol-2-yl, naphtho[2,1-d]thiazol-2-yl,        naphtho[1,2-d]imidazol-2-yl, naphtho[1,2-b]furan-2-yl or        naphtho[2,1-b]furan-2-yl group,    -   or a furo[3,2-c]isoquinolin-5-yl, pyrazolo[1,5-c]quinazolin-5-yl        or 1H-perimidin-2-yl group,    -   while the benzo groups of the above mentioned radicals R_(a) are        substituted by the groups R¹⁰ to R¹³ and the alkylene units of        the above mentioned groups R_(a) may be substituted by one or        two fluorine atoms or one or two methyl groups and the imino        groups of the above mentioned radicals R_(a) may be substituted        by a methyl group and        -   R¹⁰ denotes a hydrogen atom,        -   a fluorine, chlorine, bromine or iodine atom,        -   a methyl or ethyl group,        -   a hydroxy, methoxy or ethoxy group or        -   a difluoromethyl, trifluoromethyl, difluoromethoxy, or            trifluoromethoxy group and        -   R¹¹, R¹² and R¹³, which may be identical or different, each            denote a hydrogen, fluorine, chlorine or bromine atom or a            methyl, trifluoromethyl or methoxy group,            R² denotes a hydrogen atom or            a methyl, cyanomethyl, trifluoromethyl, ethyl,            2-cyano-ethyl, propyl, cyclopropyl or isopropyl group,            Y denotes a nitrogen atom or a group of formula C—R⁵,    -   while R⁵ denotes a hydrogen atom or a methyl, ethyl, propyl or        isopropyl group,        R³ denotes a 2-buten-1-yl or 3-methyl-2-buten-1-yl group,        a 1-buten-1-yl group,        a 2-butyn-1-yl group or        a 1-cyclopenten-1-ylmethyl group        and        R⁴ denotes a (3-amino-piperidin-1-yl) group,        the tautomers, enantiomers, diastereomers, the mixtures thereof        and the salts thereof.

Most particularly preferred are those compounds of the above generalformula I wherein

R¹ denotes a 4-oxo-3,4-dihydro-quinazolin-2-ylmethyl group,a dibenzo[b,f][1,4]oxazepin-11-ylmethyl group,a phenanthridin-6-ylmethyl group,a phenanthren-9-ylmethyl group ora naphtho[1,2-d]oxazol-2-ylmethyl or naphtho[2,1-d]oxazol-2-ylmethylgroup,R² denotes a hydrogen atom or a methyl group,Y denotes a nitrogen atom,R³ denotes a 2-butyn-1-yl groupandR⁴ denotes a (3-amino-piperidin-1-yl) group,the tautomers, enantiomers, diastereomers, the mixtures thereof and thesalts thereof.

The following compounds of general formula I deserve special mention:

-   (1)    2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(dibenzo[b,f][1,4]oxazepin-11-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

-   (2)    2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(phenanthridin-6-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

-   (3)    2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(phenanthren-9-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

-   (4)    2-((R)-3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(phenanthridin-6-yl)methyl]-7-methyl-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

-   (5)    2-((R)-3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(dibenzo[b,f][1,4]oxazepin-11-yl)methyl]-7-methyl-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

-   (6)    2-((S)-3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(dibenzo[b,f][1,4]oxazepin-11-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

-   (7)    2-((R)-3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(dibenzo[b,f][1,4]oxazepin-11-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

-   (8)    2-((R)-3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(naphtho[2,1-d]oxazol-2-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

-   (9)    2-((R)-3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(naphtho[1,2-d]oxazol-2-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

-   (10)    2-((R)-3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(4-oxo-3,4-dihydro-quinazolin-2-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

the enantiomers, the mixtures thereof and the salts thereof.According to the invention the compounds of general formula I areobtained by methods known per se, for example by the following methods:a) deprotecting a compound of general formula

wherein R¹, R², Y and R³ are as hereinbefore defined andR⁴″ denotes one of the groups mentioned for R⁴ hereinbefore whichcontain an imino, amino or alkylamino group, while the imino, amino oralkylamino group is substituted by a protective group.

The liberating of an amino group from a protected precursor is astandard reaction in synthetic organic chemistry. There are manyexamples of suitable protective groups. A summary of the chemistry ofprotective groups can be found in Theodora W. Greene and Peter G. M.Wuts, Protective Groups in Organic Synthesis, Second Edition, 1991,published by John Wiley and Sons, and in Philip J. Kocienski, ProtectingGroups, published by Georg Thieme, 1994.

The following are examples of protective groups:

the tert.-butyloxycarbonyl group which can be cleaved by treating withan acid such as for example trifluoroacetic acid or hydrochloric acid orby treating with bromotrimethylsilane or iodotrimethylsilane, optionallyusing a solvent such as methylene chloride, ethyl acetate, dioxane,methanol, isopropanol or diethylether at temperatures between 0° C. and80° C.,the 2,2,2-trichloroethoxycarbonyl group which can be cleaved by treatingwith metals such as for example zinc or cadmium in a solvent such asacetic acid or a mixture of tetrahydrofuran and a weak aqueous acid attemperatures between 0° C. and the boiling temperature of the solventused andthe carbobenzyloxycarbonyl group which can be cleaved for example byhydrogenolysis in the presence of a noble metal catalyst such as forexample palladium-charcoal and a solvent such as for example alcohols,ethyl acetate, dioxane, tetrahydrofuran or mixtures of these solvents attemperatures between 0° C. and the boiling point of the solvent, bytreating with boron tribromide in methylene chloride at temperaturesbetween −20° C. and ambient temperature, or by treating with aluminiumchloride/anisol at temperatures between 0° C. and ambient temperature.

Moreover, the compounds of general formula I obtained may be resolvedinto their enantiomers and/or diastereomers, as mentioned hereinbefore.Thus, for example, cis/trans mixtures may be resolved into their cis andtrans isomers, and compounds with at least one stereocentre may beseparated into their enantiomers.

Thus, for example, the cis/trans mixtures obtained may be resolved bychromatography into the cis and trans isomers thereof, the compounds ofgeneral formula I obtained which occur as racemates may be separated bymethods known per se (cf. Allinger N. L. and Eliel E. L. in “Topics inStereochemistry”, Vol. 6, Wiley Interscience, 1971) into their opticalantipodes and compounds of general formula I with at least 2 asymmetriccarbon atoms may be resolved into their diastereomers on the basis oftheir physical-chemical differences using methods known per se, e.g. bychromatography and/or fractional crystallisation, and, if thesecompounds are obtained in racemic form, they may subsequently beresolved into the enantiomers as mentioned above.

The enantiomers are preferably separated by column separation on chiralphases or by recrystallisation from an optically active solvent or byreacting with an optically active substance which forms salts orderivatives such as e.g. esters or amides with the racemic compound,particularly acids and the activated derivatives or alcohols thereof,and separating the diastereomeric mixture of salts or derivatives thusobtained, e.g. on the basis of their differences in solubility, whilstthe free antipodes may be released from the pure diastereomeric salts orderivatives by the action of suitable agents. Optically active acids incommon use are e.g. the D- and L-forms of tartaric acid ordibenzoyltartaric acid, di-O-p-toluoyltartaric acid, malic acid,mandelic acid, camphorsulphonic acid, glutamic acid, aspartic acid orquinic acid. An optically active alcohol may be for example (+)- or(−)-menthol and an optically active acyl group in amides, for example,may be a (+)- or (−)-menthyloxycarbonyl.

Furthermore, the compounds of formula I obtained may be converted intothe salts thereof, particularly for pharmaceutical use into thephysiologically acceptable salts with inorganic or organic acids. Acidswhich may be used for this purpose include for example hydrochloricacid, hydrobromic acid, sulphuric acid, methanesulphonic acid,phosphoric acid, fumaric acid, succinic acid, lactic acid, citric acid,tartaric acid or maleic acid.

Moreover, if the new compounds of formula I thus obtained contain acarboxy group, they may subsequently, if desired, be converted into thesalts thereof with inorganic or organic bases, particularly forpharmaceutical use into the physiologically acceptable salts thereof.Suitable bases for this purpose include for example sodium hydroxide,potassium hydroxide, arginine, cyclohexylamine, ethanolamine,diethanolamine and triethanolamine.

The compounds of general formula II used as starting materials areeither known from the literature or may be obtained by methods knownfrom the literature (cf. Examples I to XVI).

As already mentioned hereinbefore, the compounds of general formula Iaccording to the invention and the physiologically acceptable saltsthereof have valuable pharmacological properties, particularly aninhibiting effect on the enzyme DPP-IV.

The biological properties of the new compounds were investigated asfollows:

The ability of the substances and their corresponding salts to inhibitthe DPP-IV activity can be demonstrated in a test set-up in which anextract of human colon carcinoma cell line Caco-2 is used as the DPP IVsource. The differentiation of the cells in order to induce the DPP-IVexpression was carried out as described by Reiher et al. in an articleentitled “Increased expression of intestinal cell line Caco-2”, whichappeared in Proc. Natl. Acad. Sci. Vol. 90, pages 5757-5761 (1993). Thecell extract was obtained from cells solubilised in a buffer (10 mM TrisHCl, 0.15 M NaCl, 0.04 t.i.u. aprotinin, 0.5% Nonidet-P40, pH 8.0) bycentrifuging at 35,000 g for 30 minutes at 4° C. (to remove celldebris).

The DPP-IV assay was carried out as follows:

50 μl substrate solution (AFC; AFC is amido-4-trifluoromethylcoumarin),final concentration 100 μM, were placed in black microtitre plates. 20μl of assay buffer (final concentrations 50 mM Tris HCl pH 7.8, 50 mMNaCl, 1% DMSO) was pipetted in. The reaction was started by adding 30 μlof solubilised Caco-2 protein (final concentration 0.14 μg of proteinper well). The test substances to be investigated were typically addedprediluted in 20 μl, and the volume of assay buffer was then reducedaccordingly. The reaction was carried out at ambient temperature,incubating for 60 minutes. Then the fluorescence was measured in aVictor 1420 Multilabel Counter, the excitation wavelength being 405 nmand the emission wavelength being 535 nm. Blank readings (correspondingto 0% activity) were obtained in mixtures without any Caco-2 protein(volume replaced by assay buffer), control values (corresponding to 100%activity) were obtained in mixtures with no substance added. The potencyof the test substances in question, expressed as IC₅₀ values, wascalculated from dosage/activity curves consisting of 11 measuring pointsin each case. The following results were obtained:

Compound DPP IV inhibition (Example No.) IC₅₀ [nM] 1 14 1(1) 17 1(2) 581(3) 8 1(4) 9 1(7) 3 1(8) 7 1(9) 3

The compounds prepared according to the invention are well tolerated, asfor example when 10 mg/kg of the compound of Example 1 were administeredto rats by oral route no changes in the animals' behaviour could bedetected.

In view of their ability to inhibit DPP-IV activity, the compounds ofgeneral formula I according to the invention and the correspondingpharmaceutically acceptable salts thereof are suitable for treating allthose conditions or illnesses which can be influenced by the inhibitionof the DPP-IV activity. It is therefore to be expected that thecompounds according to the invention will be suitable for the preventionor treatment of diseases or conditions such as type I and type IIdiabetes mellitus, diabetic complications, metabolic acidosis orketosis, insulin resistance, dyslipidaemias of various origins,arthritis, atherosclerosis and related diseases, obesity, allografttransplantation and calcitonin-induced osteoporosis. In addition thesesubstances are capable of preventing B-cell degeneration such as e.g.apoptosis or necrosis of pancreatic B-cells. The substances are alsosuitable for improving or restoring the function of pancreatic cells andalso increasing the number and size of pancreatic B-cells. Additionally,and on the basis of the role of the Glucagon-Like Peptides, such as e.g.GLP-1 and GLP-2 and their link with DPP-IV inhibition, it is likely thatthe compounds according to the invention are suitable for achieving,inter alia, a sedative or anxiety-relieving effect and also offavourably affecting catabolic states after operations or hormonalstress responses or of reducing mortality or morbidity after myocardialinfarct. They are also suitable for treating all conditions which areconnected with the above mentioned effects and which are mediated byGLP-1 or GLP-2. The compounds according to the invention may also beused as diuretics or antihypertensives and are suitable for preventingand treating acute renal failure. They are also suitable for theprevention and treatment of chronic inflammatory intestinal diseases. Itis also expected that DPP-IV inhibitors and hence also the compoundsaccording to the invention may be used to treat infertility or toimprove fertility in humans or mammals, particularly when theinfertility is connected with insulin resistance or polycystic ovarysyndrome. The substances are also suitable for treating deficiencies ofgrowth hormone which are associated with reduced stature.

The compounds according to the invention may also be used in conjunctionwith other active substances. Therapeutic agents which are suitable forsuch combinations include, for example, antidiabetics, such asmetformin, sulphonylureas (e.g. glibenclamide, tolbutamide,glimepiride), nateglinide, repaglinide, thiazolidinedione (e.g.rosiglitazone, pioglitazone), PPAR-gamma agonists (e.g. GI 262570),alpha-glucosidase inhibitors (e.g. acarbose, voglibose), alpha2antagonists, insulin and insulin analogues, GLP-1 and GLP-1 analogues(e.g. exendin-4) or amylin. Also, inhibitors of protein tyrosinephosphatase 1, substances which influence deregulated glucose productionin the liver, such as e.g. inhibitors of glucose-6-phosphatase, orfructose-1,6-bisphosphatase, glycogen phosphorylase, glucagon receptorantagonists and inhibitors of phosphoenol pyruvate carboxykinase,glycogen synthase kinase or pyruvate dehydrokinase, lipid loweringagents, such as HMG-CoA-reductase inhibitors (e.g. simvastatin,atorvastatin), fibrates (e.g. bezafibrate, fenofibrate), nicotinic acidand its derivatives, cholesterol absorption inhibitors such as forexample ezetimibe, bile acid-binding substances such as for examplecholestyramine, HDL-raising compounds such as for example inhibitors ofCETP or regulators of ABC1 or active substances for the treatment ofobesity, such as e.g. sibutramine or tetrahydrolipostatin, orβ₃-agonists such as SB-418790 or AD-9677.

It is also possible to combine the compounds with drugs for treatinghigh blood pressure such as e.g. AII antagonists or ACE inhibitors,diuretics, β-blockers, etc., or combinations thereof.

The dosage required to achieve such an effect is expediently, byintravenous route, 1 to 100 mg, preferably 1 to 30 mg, and by oral route1 to 1000 mg, preferably 1 to 100 mg, in each case 1 to 4 times a day.For this purpose, the compounds of formula I prepared according to theinvention, optionally combined with other active substances, may beincorporated together with one or more inert conventional carriersand/or diluents, e.g. with corn starch, lactose, glucose,microcrystalline cellulose, magnesium stearate, polyvinylpyrrolidone,citric acid, tartaric acid, water, water/ethanol, water/glycerol,water/sorbitol, water/polyethylene glycol, propylene glycol,cetylstearyl alcohol, carboxymethylcellulose or fatty substances such ashard fat or suitable mixtures thereof into conventional galenicpreparations such as plain or coated tablets, capsules, powders,suspensions or suppositories.

The Examples that follow are intended to illustrate the invention:

Preparation of the starting compounds:

EXAMPLE I2-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-3-(2-butyn-1-yl)-5-[(dibenzo[b,f][1,4]-oxazepin-11-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

317 mg 11-chloromethyl-dibenzo[b,f][1,4]oxazepin are added to 400 mg2-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-3-(2-butyn-1-yl)-3,5-dihydro-imidazo[4,5-d]pyridazin-4-oneand 276 mg potassium carbonate in 4 ml N,N-dimethylformamide. Thereaction mixture is stirred for two hours at 80° C. For working up it iscombined with water and the precipitate formed is suction filtered. Thecrude product is purified by chromatography over a silica gel columnwith methylene chloride/methanol (100:0 to 70:30) as eluant.

Yield: 120 mg (20% of theory)

Mass spectrum (ESI⁺): m/z=594 [M+H]⁺

The following compounds are obtained analogously to Example I:

-   (1)    2-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-3-(2-butyn-1-yl)-5-[(phenanthridin-6-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one-   (2)    2-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-3-(2-butyn-1-yl)-5-[(phenanthren-9-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one-   (3)    2-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-3-(2-butyn-1-yl)-5-[(phenanthridin-6-yl)methyl]-7-methyl-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

R_(f) value: 0.41 (silica gel, cyclohexane/ethyl acetate=3:7)

Mass spectrum (ESI⁺): m/z=592 [M+H]⁺

-   (4)    2-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-3-(2-butyn-1-yl)-5-[(dibenzo[b,f][1,4]oxazepin-11-yl)methyl]-7-methyl-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

R_(f) value: 0.50 (silica gel, cyclohexane/ethyl acetate=2:8)

Mass spectrum (ESI⁺): m/z=608 [M+H]⁺

-   (5)    2-bromo-3-(2-butyn-1-yl)-5-[(dibenzo[b,f][1,4]oxazepin-11-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

Mass spectrum (ESI⁺): m/z=474, 476 [M+H]⁺

-   (6)    2-bromo-3-(2-butyn-1-yl)-5-[(naphtho[2,1-d]oxazol-2-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

R_(f) value: 0.80 (silica gel, methylene chloride/ethanol=9:1)

-   (7)    2-bromo-3-(2-butyn-1-yl)-5-[(naphtho[1,2-d]oxazol-2-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

R_(f) value: 0.50 (silica gel, methylene chloride/methanol=19:1)

-   (8)    2-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-3-(2-butyn-1-yl)-5-cyanomethyl-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

R_(f) value: 0.40 (silica gel, petroleum ether/ethyl acetate=1:4)

Mass spectrum (ESI⁺): m/z=426 [M+H]⁺

EXAMPLE II2-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-3-(2-butyn-1-yl)-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

2.50 g 3-(tert.-butyloxycarbonylamino)-piperidine are added to 2.65 g2-bromo-3-(2-butyn-1-yl)-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one and2.12 g sodium carbonate in 5 ml dimethylsulphoxide. The reaction mixtureis stirred overnight at 85° C.

After cooling to ambient temperature it is combined with water andextracted with ethyl acetate. The combined organic phases are dried overmagnesium carbonate and evaporated down. The crude product is furtherreacted without any further purification.

Mass spectrum (ESI⁺): m/z=387 [M+H]⁺

The following compounds are obtained analogously to Example II:

-   (1)    2-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-3-(2-butyn-1-yl)-7-methyl-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

R_(f) value: 0.15 (silica gel, cyclohexane/ethyl acetate=3:7)

Mass spectrum (ESI⁺): m/z=401 [M+H]⁺

-   (2)    2-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-3-(2-butyn-1-yl)-5-[(dibenzo[b,f][1,4]oxazepin-11-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

Mass spectrum (ESI⁺): m/z=594 [M+H]⁺

-   (3)    2-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-3-(2-butyn-1-yl)-5-[(dibenzo[b,f][1,4]oxazepin-11-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

Mass spectrum (ESI⁺): m/z=594 [M+H]⁺

-   (4)    2-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-3-(2-butyn-1-yl)-5-[(naphtho[2,1-d]oxazol-2-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

R_(f) value: 0.70 (silica gel, methylene chloride/ethanol=9:1)

-   (5)    2-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-3-(2-butyn-1-yl)-5-[(naphtho[1,2-d]oxazol-2-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

R_(f) value: 0.65 (silica gel, methylene chloride/methanol=9:1)

Mass spectrum (ESI⁺): m/z=568 [M+H]⁺

-   (6)    2-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-3-(2-butyn-1-yl)-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

Mass spectrum (ESI⁺): m/z=387 [M+H]⁺

R_(f) value: 0.50 (silica gel, methylene chloride/ethanol=9:1)

EXAMPLE III2-bromo-3-(2-butyn-1-yl)-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

0.63 ml hydrazine hydrate are added dropwise to 3.68 g methyl2-bromo-3-(2-butyn-1-yl)-5-formyl-3H-imidazole-4-carboxylate in 50 ml ofethanol. The reaction mixture is stirred for one hour at ambienttemperature, then 3 ml acetic acid are added and the reaction mixture isrefluxed for a further hour. The precipitate formed is suction filtered,washed with ethanol and diethyl ether and dried.

Yield: 2.65 g (77% of theory)

Mass spectrum (ESI⁺): m/z=267, 269 [M+H]⁺

EXAMPLE IV methyl2-bromo-3-(2-butyn-1-yl)-5-formyl-3H-imidazole-4-carboxylate

45 ml diisobutylaluminum hydride solution (1M in toluene) are addeddropwise to 12.45 g dimethyl2-bromo-3-(2-butyn-1-yl)-1H-imidazole-4,5-dicarboxylate in 150 ml oftetrahydrofuran under an argon atmosphere at −65° C. The reactionmixture is stirred for two hours at −65° C., then another 9 mldiisobutylaluminum hydride solution are added. After another hour thereaction mixture is quenched at −65° C. with a mixture of 1 Mhydrochloric acid and tetrahydrofuran (1:1) and stirred for ten minutes.Then the cooling bath is removed, the reaction mixture is diluted withwater and extracted with ethyl acetate. The combined organic phases aredried over magnesium sulphate and evaporated down. The crude product ispurified by chromatography over a silica gel column withcyclohexane/ethyl acetate (2:1 to 1:1).

Yield: 9.58 g (85% of theory)

Mass spectrum (ESI⁺): m/z=285, 287 [M+H]⁺

The following compounds are obtained analogously to Example IV:

-   (1) methyl    2-bromo-3-(3-methyl-2-buten-1-yl)-5-formyl-3H-imidazole-4-carboxylate

Mass spectrum (ESI⁺): m/z=301, 303 [M+H]⁺

EXAMPLE V dimethyl2-bromo-3-(2-butyn-1-yl)-1H-imidazole-4,5-dicarboxylate

4.53 ml of 1-bromo-2-butyne are added to 13.20 g dimethyl2-bromo-1H-imidazole-4,5-dicarboxylate and 8.57 g potassium carbonate in70 ml N,N-dimethylformamide and the reaction mixture is stirredovernight at ambient temperature.

For working up it is combined with water and extracted with ethylacetate. The combined organic phases are dried over magnesium sulphateand evaporated down.

Yield: 14.58 g (92% of theory)

Mass spectrum (ESI⁺): m/z=315, 317 [M+H]⁺

The following compounds are obtained analogously to Example V:

-   (1) dimethyl    2-bromo-3-(3-methyl-2-buten-1-yl)-1H-imidazole-4,5-dicarboxylate

Mass spectrum (ESI⁺): m/z=331, 333 [M+H]⁺

EXAMPLE VI Dimethyl 2-bromo-1H-imidazole-4,5-dicarboxylate

6.11 ml bromine are added to 19.80 g dimethyl1H-imidazole-4,5-dicarboxylate and 14.92 g potassium carbonate in 600 mlmethylene chloride. The reaction mixture is stirred for one hour atambient temperature, then a mixture of saturated sodium sulphitesolution and saturated sodium chloride solution (1:1) is added. Theorganic phase is largely separated off and the aqueous phase isextracted with ethyl acetate several times. The combined organic phasesare dried over magnesium sulphate and evaporated down, leaving about7.40 g crude product. The aqueous phase is combined with ethyl acetateand extracted overnight in an extraction apparatus. The ethyl acetateextract is evaporated down and the flask residue is combined with thecrude product already obtained.

Yield: 13.10 g (46% of theory)

Mass spectrum (ESI⁺): m/z=263, 265 [M+H]⁺

EXAMPLE VII2-Bromo-3-(2-butyn-1-yl)-7-methyl-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

0.50 ml of 1-bromo-2-butyne are added to 1.30 g2-bromo-7-methyl-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one and 0.99 mlHünig base in 30 ml of N,N-dimethylformamide. The reaction mixture isstirred for three hours at ambient temperature. Then the solvent isdistilled off in vacuo using the rotary evaporator. The flask residue isstirred with 40 ml of water and 0.5 ml concentrated aqueous ammoniasolution, suction filtered and washed with ethanol as well as diethylether.

Yield: 1.30 g (82% of theory)

R_(f) value: 0.60 (silica gel, cyclohexane/ethyl acetate=3:7)

Mass spectrum (ESI⁺): m/z=281, 283 [M+H]⁺

EXAMPLE VIII 2-bromo-7-methyl-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

5.20 ml of a 1.8 M solution of bromine in acetonitrile are slowly addeddropwise to 1.40 g of 7-methyl-3,5-dihydro-imidazo[4,5-d]pyridazin-4-oneand 1.30 g potassium carbonate in 40 ml acetonitrile. Then the reactionmixture is heated to 70° C., whereupon the mixture is rapidlydecolourised. More bromine solution and potassium carbonate are addedbatchwise until the reaction has ended, according to HPLC-MS. Forworking up the reaction mixture is evaporated down, stirred with 100 mlof water and suction filtered. The filtrate is acidified with 1 Mhydrochloric acid and extracted with ethyl acetate. The combinedextracts are dried over sodium sulphate and evaporated down.

Yield: 1.30 g (61% of theory)

R_(f) value: 0.37 (silica gel, methylene chloride/methanol=9:1)

Mass spectrum (ESI⁺): m/z=229, 231 [M+H]⁺

EXAMPLE IX 7-methyl-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

A solution of 4.00 g sodium nitrite in 15 ml of water is added dropwiseat 50° C. to 2.20 g of 4-amino-7-methyl-3H-imidazo[4,5-d]pyridazine in amixture of 30 ml acetic acid, 5 ml of water and 0.5 ml concentratedsulphuric acid. The reaction mixture is stirred for a further two hoursat 50° C. and then heated to 90° C. for one hour. After cooling toambient temperature the reaction mixture is diluted with 30 ml of water.The precipitate formed is suction filtered, washed with water, ethanoland diethyl ether and dried.

Yield: 1.00 g (45% of theory)

Mass spectrum (ESI⁺): m/z=151 [M+H]⁺

EXAMPLE X 4-amino-7-methyl-3H-imidazo[4,5-d]pyridazine

A mixture of 2.00 g 5-acetyl-3H-imidazole-4-carbonitrile and 4.00 mlhydrazine hydrate in 50 ml of ethanol is heated to 100° C., until thereaction is complete according to HPLC-MS. After cooling to ambienttemperature the reaction mixture is evaporated down, stirred with 20 mlof cold ethanol and suction filtered. The filter cake is washed withdiethyl ether and dried.

Yield: 2.10 g (95% of theory)

Mass spectrum (ESI⁺): m/z=150 [M+H]⁺

EXAMPLE XI 5-acetyl-3H-imidazole-4-carbonitrile

57 ml of a 3 M solution of methylmagnesium bromide in diethyl ether areadded to 7.00 g of 4,5-dicyano-imidazole in 80 ml of tetrahydrofuranunder an argon atmosphere, while the temperature is maintained between5° C. and 15° C.

After two hours the reaction is complete according to thin layerchromatography and the reaction mixture is diluted with 400 ml of ethylacetate. Then 400 ml saturated ammonium chloride solution are slowlyadded. After ten minutes the mixture is acidified with semiconcentratedsulphuric acid and stirred for another twenty minutes before the organicphase is separated off. The aqueous phase is extracted with ethylacetate and the combined organic phases are dried over sodium sulphateand evaporated down. The flask residue is stirred with ethyl acetate,suction filtered and washed with ethyl acetate and diethyl ether.

Yield: 3.30 g (43% of theory)

Mass spectrum (ESI⁺): m/z=136 [M+H]⁺

EXAMPLE XII 2-chloromethyl-naphtho[2,1-d]oxazole

Prepared by reacting 2.93 g of 2-amino-1-naphthol with 3.54 g of2-chloro-1,1,1-triethoxy-ethane in 25 ml of ethanol at 60° C.

Yield: 1.90 g (58% of theory)

R_(f) value: 0.55 (silica gel, petroleum ether/ethyl acetate=9:1)

Mass spectrum (ESI⁺): m/z=218, 220 [M+H]⁺

The following compounds are obtained analogously to Example XII:

-   (1) 2-chloromethyl-naphtho[1,2-d]oxazole

R_(f) value: 0.90 (silica gel, methylene chloride/methanol=19:1)

Mass spectrum (ESI⁺): m/z=218, 220 [M+H]⁺

EXAMPLE XIII2-bromo-3-(3-methyl-2-buten-1-yl)-3,5-dihydro-imidazo[4,5-c]pyridin-4-one

1.55 g Burgess reagent(methoxycarbonylsulphamoyl-triethylammonium-N-betaine) are added to 1.60g of2-bromo-7-hydroxy-3-(3-methyl-2-buten-1-yl)-3,5,6,7-tetrahydro-imidazo[4,5-c]pyridin-4-onein 20 ml methylene chloride and 4 ml of tetrahydrofuran. The reactionmixture is stirred for eight hours at 60° C., then another 0.3equivalents Burgess reagent is added. After a further two hours thecooled reaction mixture is combined with aqueous sodium hydrogencarbonate solution and extracted with ethyl acetate. The combinedorganic phases are dried over magnesium sulphate and evaporated down.The flask residue is chromatographed through a silica gel column withmethylene chloride/methanol (1:0 to 10:1) as eluant.

Yield: 1.06 g (60% of theory)

Mass spectrum (ESI⁺): m/z=282, 284 [M+H]+

EXAMPLE XIV2-bromo-7-hydroxy-3-(3-methyl-2-buten-1-yl)-3,5,6,7-tetrahydro-imidazo[4,5-c]pyridin-4-one

90 ml of water and 5.40 g iron powder are added to 4.15 g methyl2-bromo-5-(1-hydroxy-2-nitro-ethyl)-3-(3-methyl-2-buten-1-yl)-3H-imidazole-4-carboxylatein 270 ml of ethanol. The mixture is refluxed, combined with 36 mlglacial acetic acid and stirred for one and a half hours at refluxtemperature. The cooled reaction solution is filtered through Celite.The filtrate is evaporated down, combined with ethanol and made basicwith solid potassium carbonate. The mixture is stirred for three hoursat 60° C. Then the ethanol is distilled off, the flask residue iscombined with water and extracted with ethyl acetate. The combinedextracts are dried over magnesium sulphate and evaporated down. Thecrude product is purified by chromatography over a silica gel columnwith methylene chloride/methanol (1:1 to 7:1) as eluant.

Yield: 1.62 g (47% of theory)

Mass spectrum (ESI⁺): m/z=300, 302 [M+H]⁺

EXAMPLE XV Methyl2-bromo-5-(1-hydroxy-2-nitro-ethyl)-3-(3-methyl-2-buten-1-yl)-3H-imidazole-4-carboxylate

35 ml nitromethane are added to 1.14 g caesium carbonate in 15 ml ofmethanol at ambient temperature. Then the mixture is combined with asolution of 3.50 g methyl2-bromo-3-(3-methyl-2-buten-1-yl)-5-formyl-3H-imidazole-4-carboxylate in20 ml of methanol and 5 ml methylene chloride and stirred for 15 minutesat ambient temperature. Then 0.5 ml acetic acid are added and thesolution is evaporated down in vacuo. The flask residue is combined withaqueous sodium hydrogen carbonate solution and extracted with ethylacetate. The combined organic phases are dried over magnesium sulphateand evaporated down.

Yield: 4.15 g (99% of theory)

Mass spectrum (ESI⁺): m/z=362, 364 [M+H]⁺

EXAMPLE XVI2-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-3-(2-butyn-1-yl)-5-[(4-oxo-3,4-dihydro-quinazolin-2-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

40 mg sodium methoxide (95%) are added to a solution of 605 mg2-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-3-(2-butyn-1-yl)-5-cyanomethyl-3,5-dihydro-imidazo[4,5-d]pyridazin-4-onein 9 ml of methanol. The mixture is stirred for one hour at ambienttemperature and then neutralised with 41 SL glacial acetic acid. Then asolution of 195 mg anthranilic acid in 2 ml of methanol is added and thereaction mixture is heated to 70° C. After about two hours a white,voluminous precipitate is formed and the reaction mixture is cooled toambient temperature. The precipitate formed is suction filtered, washedwith cold methanol and dried.

Yield: 234 mg (30% of theory)

Mass spectrum (ESI⁺): m/z=545 [M+H]⁺

Preparation of the final compounds:

EXAMPLE 1

2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(dibenzo[b,f][1,4]oxazepin-11-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

0.33 ml trifluoroacetic acid are added to 120 mg2-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-3-(2-butyn-1-yl)-5-[(dibenzo[b,f][1,4]oxazepin-11-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-onein 3 ml methylene chloride while cooling with an ice bath. The reactionmixture is stirred overnight at ambient temperature.

For working up it is poured onto cooled saturated potassium carbonatesolution and extracted with methylene chloride. The organic phase isseparated off and evaporated down. The crude product is purified bychromatography over a silica gel column with methylene chloride/methanol(100:0 to 70:30) as eluant.

Yield: 63 mg (63% of theory)

Mass spectrum (ESI⁺): m/z=494 [M+H]⁺

The following compounds are obtained analogously to Example 1:

-   (1)    2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(phenanthridin-6-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

Mass spectrum (ESI⁺): m/z=478 [M+H]⁺

-   (2)    2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(phenanthren-9-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

Mass spectrum (ESI⁺): m/z=477 [M+H]⁺

-   (3)    2-((R)-3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(phenanthridin-6-yl)methyl]-7-methyl-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one    x trifluoroacetic acid

R_(f) value: 0.45 (Reversed phase ready-made TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:0.1)

Mass spectrum (ESI⁺): m/z=492 [M+H]⁺

-   (4)    2-((R)-3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(dibenzo[b,f][1,4]oxazepin-11-yl)methyl]-7-methyl-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

Carried out with isopropanolic hydrochloric acid (5-6 M) in methylenechloride.

Mass spectrum (ESI⁺): m/z=508 [M+H]⁺

-   (5)    2-((S)-3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(dibenzo[b,f][1,4]oxazepin-11-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

Mass spectrum (ESI⁺): m/z=494 [M+H]⁺

-   (6)    2-((R)-3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(dibenzo[b,f][1,4]oxazepin-11-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

Mass spectrum (ESI⁺): m/z=494 [M+H]⁺

-   (7)    2-((R)-3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(naphtho[2,1-d]oxazol-2-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

R_(f) value: 0.40 (silica gel, methylene chloride/ethanol/conc. aqueousammonia=90:10:2)

Mass spectrum (ESI⁺): m/z=468 [M+H]⁺

-   (8)    2-((R)-3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(naphtho[1,2-d]oxazol-2-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

Mass spectrum (ESI⁺): m/z=468 [M+H]⁺

-   (9)    2-((R)-3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(4-oxo-3,4-dihydro-quinazolin-2-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

Mass spectrum (ESI⁺): m/z=445 [M+H]⁺

The following compounds may also be obtained analogously to theforegoing Examples and other methods known from the literature:

No. Name Structural formula  (1)2-(3-amino-piperidin-1-yl)-3-(2-buten-1-yl)-5-[(3,4-dihydro-quinolin-2-yl)methyl]-6,7-dimethyl-3,5-dihydro-imidazo[4,5-c]pyridin- 4-one

 (2) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(3,4-dihydro-isoquinolin-1-yl)methyl]-7-cyclopropyl-3,5-dihydro-imidazo[4,5- d]pyridazin-4-one

 (3) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(3,3-dimethyl-3,4-dihydro-isoquinolin-1-yl)methyl]-3,5-dihydro-imidazo[4,5- d]pyridazin-4-one

 (4) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(4,4-dimethyl-3,4-dihydro-isoquinolin-1-yl)methyl]-3,5-dihydro-imidazo[4,5- d]pyridazin-4-one

 (5) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(1-methyl-1,4-dihydro-quinazolin-2-yl)methyl]-3,5-dihydro-imidazo[4,5- d]pyridazin-4-one

 (6) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(1-methyl-4-oxo-1,4-dihydro-quinazolin-2-yl)methyl]3,5-dihydro-imidazo[4,5- d]pyridazin-4-one

 (7) 2-(3-amino-piperidin-1-yl)-3-(2-buten-1-yl)-5-[(5,6,7,8-tetrafluoro-1-methyl-1,4-dihydro-quinazolin-2-yl)methyl]-3,5-dihydro- imidazo[4,5-c]pyridin-4-one

 (8) 2-(3-amino-piperidin-1-yl)-3-(2-buten-1-yl)-5-[(3,4-dihydro-quinazolin-2-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

 (9) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(3-methyl-3,4-dihydro-quinazolin-2-yl)methyl]-3,5-dihydro-imidazo[4,5- d]pyridazin-4-one

(10) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(3-methyl-3,4-dihydro-quinazolin-2-yl)methyl]-3,5-dihydro-imidazo[4,5- d]pyridin-4-one

(11) 2-(3-amino-piperidin-1-yl)-3-(1-buten-1-yl)-5-[(1H-benzo[d][1,2]oxazin-4-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

(12) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(1-oxo-1H-benzo[d][1,2]oxazin-4- yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

(13) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(4H-benzo[e][1,3]oxazin-2-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

(14) 2-(3-amino-piperidin-1-yl)-3-(2-buten-1-yl)-5-[(4,4-dimethyl-4H-benzo[e][1,3]oxazin-2-yl)methyl]-3,5-dihydro-imidazo[4,5- d]pyridazin-4-one

(15) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(4-oxo-4H-benzo[e][1,3]oxazin-2- yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

(16) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(4H-benzo[d][1,3]oxazin-2-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

(17) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(4H-benzo[d][1,3]oxazin-2-yl)methyl]-7-methyl-3,5-dihydro-imidazo[4,5-c]pyridin-4- one

(19) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(4,4-dimethyl-4H-benzo[d][1,3]oxazin-2-yl)methyl]-3,5-dihydro-imidazo[4,5- d]pyridazin-4-one

(20) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(4-oxo-4H-benzo[d][1,3]oxazin-2- yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

(21) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(2H-benzo[1,4]oxazin-3-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

(22) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(2-oxo-2H-benzo[1,4]oxazin-3- yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

(23) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(2,2-dimethyl-2H-benzo[1,4]oxazin-3-yl)methyl]-3,5-dihydro-imidazo[4,5- d]pyridazin-4-one

(24) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[4H-benzo[e][1,3]thiazin-2-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

(25) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[4,4-dimethyl-4H-benzo[e][1,3]thiazin-2-yl)methyl]-3,5-dihydro-imidazo[4,5- d]pyridazin-4-one

(26) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[4-oxo-4H-benzo[e][1,3]thiazin-2- yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

(27) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(4H-benzo[d][1,3]thiazin-2-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

(28) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(2H-benzo[1,4]thiazin-3-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

(29) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(2-oxo-2H-benzo[e][1,3]oxazin-4- yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

(30) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(1-methyl-2,2-dioxo-1H- benzo[c][1,2]thiazin-4-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

(31) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(2,3-dihydro-1H-benzo[e][1,4]diazepin-5-yl)methyl]-3,5-dihydro-imidazo[4,5- d]pyridazin-4-one

(32) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(2-oxo-2,3-dihydro-1H- benzo[e][1,4]diazepin-5-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

(33) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(1-methyl-2,3-dihydro-1H- benzo[e][1,4]diazepin-5-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

(34) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(1-methyl-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-5-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

(35) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(4-oxo-4,5-dihydro-3H- benzo[b][1,4]diazepin-2-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

(36) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(5-methyl-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

(37) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[5-oxo-4,5-dihydro-3H- benzo[e][1,4]diazepin-2-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

(38) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[4-methyl-5-oxo-4,5-dihydro-3H-benzo[3][1,4]diazepin-2-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

(39) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(2,3-dihydro-benzo[f][1,4]oxazepin-5-yl)methyl]-3,5-dihydro-imidazo[4,5- d]pyridazin-4-one

(40) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(3,3-dimethyl-2,3-dihydro- benzo[f][1,4]oxazepin-5-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

(41) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(2,2-dimethyl-2,3-dihydro- benzo[f][1,4]oxazepin-5-yl)methyl]-7-methyl-3,5-dihydro-imidazo[4,5-d]pyridazin- 4-one

(42) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(2,3-dihydro-benzo[b][1,4]oxazepin-4-yl)methyl]-7-methyl-3,5-dihydro- imidazo[4,5-d]pyridazin-4-one

(43) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(6,6-dimethyl-2,3-dihydro- benzo[b][1,4]oxazepin-4-yl)methyl]-7-methyl-3,5-dihydro-imidazo[4,5-d]pyridazin- 4-one

(44) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(2,3-dihydro-benzo[b][1,4]thiazepin-4-yl)methyl]-7-methyl-3,5-dihydro- imidazo[4,5-d]pyridazin-4-one

(45) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(2,2-dimethyl-2,3-dihydro- benzo[b][1,4]thiazepin-4-yl)methyl]-7-methyl-3,5-dihydro-imidazo[4,5-d]pyridazin- 4-one

(46) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(2,3-dihydro-benzo[f][1,4]thiazepin-5-yl)methyl]-7-methyl-3,5-dihydro- imidazo[4,5-d]pyridazin-4-one

(47) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)- 5-[(5-oxo-4,5-dihydro-benzo[f][1,3,4]oxadiazepin-2-yl)methyl]-7-methyl-3,5-dihydro-imidazo[4,5-d]pyridazin- 4-one

(48) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(11H-dibenzo[b,e]azepin-6-yl)methyl]-7-ethyl-3,5-dihydro-imidazo[4,5-d]pyridazin-4- one

(49) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(11H-dibenzo[b,e]azepin-6-yl)methyl]-7-cyanomethyl-3,5-dihydro-imidazo[4,5- d]pyridazin-4-one

(50) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(11,11-difluoro-11H-dibenzo[b,e]azepin-6-yl)methyl]-3,5-dihydro-imidazo[4,5- c]pyridin-4-one

(51) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(11-oxo-11H-dibenzo[b,e]azepin-6-yl)methyl]-7-(2-cyanoethyl)-3,5-dihydro- imidazo[4,5-d]pyridazin-4-one

(52) 2-(3-amino-piperidin-1-yl)-3-(1-buten-1-yl)-5-[(11H-benzo[e]pyrido[3,2-b]azepin-6- yl)methyl]-7-methyl-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

(53) 2-(3-amino-piperidin-1-yl-(2-butyn-1-yl)-5-[(5H-1,9,10-triaza-dibenzo[a,d]cyclohepten-11-yl)methyl]-3,5-dihydro-imidazo[4,5- d]pyridin-4-one

(54) 2-(3-amino-piperidin-1-yl)-3-(2-buten-1-yl)-5-[(5-methyl-5H-dibenzo[b,e][1,4]diazepin-11-yl)methyl]-7-methyl-3,5-dihydro- imidazo[4,5-d]pyridazin-4-one

(55) 2-(3-amino-piperidin-1-yl)-3-(1-buten-1-yl)-5-[(dibenzo[b,f][1,4]oxazepin-11-yl)methyl]-3,5-dihydro-imidazo[4,5-c]pyridin-4-one

(56) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(dibenzo[b,f][1,4]thiazepin-11-yl)methyl]-7-methyl-3,5-dihydro-imidazo[4,5- d]pyridazin-4-one

(57) 2-(3-amino-piperidin-1-yl)-3-(1-buten-1-yl)-5-[(dibenzo[b,f][1,4]thiazepin-11-yl)methyl]-3,5-dihydro-imidazo[4,5-c]pyridin-4-one

(58) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(5-oxo-dibenzo[b,f][1,4]thiazepin-11-yl)methyl]-7-methyl-3,5-dihydro- imidazo[4,5-d]pyridazin-4-one

(59) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(5,5-dioxo-dibenzo[b,f][1,4]-thiazepin-11-yl)methyl]-7-methyl-3,5-dihydro- imidazo[4,5-d]pyridazin-4-one

(60) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(5H-dibenzo[a,d]cyclohepten-10- yl)methyl]-7-methyl-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

(61) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(5-methyl-5H-dibenzo[b,f]azepin-10-yl)methyl]-7-trifluoromethyl-3,5-dihydro- imidazo[4,5-d]pyridazin-4-one

(62) 2-(3-amino-piperidin-1-yl)-3-(3-methyl-2-buten-1-yl)-5-[(phenanthridin-6-yl)methyl]-7-methyl-3,5-dihydro-imidazo[4,5- d]pyridazin-4-one

(63) 2-(3-amino-piperidin-1-yl)-3-(2-buten-1-yl)-5-[(phenanthridin-6-yl)methyl]-7-methyl-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

(64) 2-(3-amino-piperidin-1-yl)-3-(1-buten-1-yl)-5-[(phenanthridin-6-yl)methyl]-7-methyl-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

(65) 2-(3-amino-piperidin-1-yl)-3-[(1-cyclopenten-1-yl)methyl]-5-[(phenanthridin-6-yl)methyl]-7-methyl-3,5-dihydro- imidazo[4,5-d]pyridazin-4-one

(66) 2-(3-amino-piperidin-1-yl)-3-(1-buten-1-yl)-5-[(phenanthridin-6-yl)methyl]-3,5-dihydro- imidazo[4,5-c]pyridin-4-one

(67) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(benzo[c][1,5]naphthyridin-6-yl)methyl]-7-cyclopropyl-3,5-dihydro-imidazo[4,5- d]pyridazin-4-one

(68) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(benzo[h][1,6]naphthyridin-5-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

(69) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(benzo[c][1,8]naphthyridin-6-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

(70) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(5-benzo[f][1,7]naphthyridin-5- yl)methyl]-3,5-dihydro-imidazo[4,5-c]pyridin-4-one

(71) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(1,5,9-triaza-phenanthren-10-yl)methyl]-3,5-dihydro-imidazo[4,5-c]pyridin-4-one

(72) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(1,2,3,4-tetrahydrophenanthridin-6-yl)methyl]-3,5-dihydro-imidazo[4,5- c]pyridin-4-one

(73) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(1,2,3,4,4a,10b-hexahydro-phenanthridin-6-yl)methyl]-3,5-dihydro-imidazo[4,5- c]pyridin-4-one

(74) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(2,3-dihydro-1H-4-aza- cyclopenta[a]naphth-5-yl)methyl]-3,5-dihydro-imidazo[4,5-c]pyridin-4-one

(75) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(8,9,10,11-tetrahydro-7H-6-aza- cyclohepta[a]naphth-5-yl)methyl]-3,5-dihydro-imidazo[4,5-c]pyridin-4-one

(76) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(2,3-dihydro-1H-4-oxo-10-aza- phenanthren-9-yl)methyl]-3,5-dihydro-imidazo[4,5-c]pyridin-4-one

(77) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(1-oxo-2,3-dihydro-1H-4-oxo-10-aza-phenanthren-9-yl)methyl]-3,5-dihydro- imidazo[4,5-c]pyridin-4-one

(78) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(10-cyanophenanthren-9-yl)methyl]-3,5-dihydro-imidazo[4,5-c]pyridin-4-one

(79) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(benzo[h]quinolin-6-yl)methyl]-3,5-dihydro-imidazo[4,5-c]pyridin-4-one

(80) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(benzo[f]quinolin-6-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

(81) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(benzo[f]quinoxalin-6-)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

(82) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(5H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-11-yl)methyl]-7-methyl-3,5-dihydro- imidazo[4,5-d]pyridazin-4-one

(83) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(thieno[3,2-b][1,4]benzoxazepin-9-yl)methyl]-7-trifluoromethyl-3,5-dihydro- imidazo[4,5-d]pyridazin-4-one

(84) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(thieno[3,2-b][1,4]benzoxazepin-9-yl)methyl]-3,5-dihydro-imidazo[4,5- c]pyridin-4-one

(85) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(5H-dibenzo[d,f][1,3]diazepin-6- yl)methyl]-7-methyl-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

(86) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(5-methyl-5H-dibenzo[d,f][1,3]diazepin-6-yl)methyl]-3,5-dihydro-imidazo[4,5- c]pyridin-4-one

(87) 2-(3-amino-piperidin-1-yl)-3-(3-methylbut-2-en-1-yl)-5-[(5-oxa-7-aza- dibenzo[a,c]cyclohepten-6-yl)methyl]-7-methyl-3,5-dihydro-imidazo[4,5-c]pyridin-4- one

(88) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(naphtho[1,2-d]thiazol-2-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

(89) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(naphtho[2,1-d]thiazol-2-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

(90) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(3H-naphtho[1,2-d]imidazol-2-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

(91) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(naphtho[1,2-b]furan-2-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

(92) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(naphtho[2,1-b]furan-2-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

(93) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(2-methyl-furo[3,2-c]isoquinolin-5-yl)methyl]-3,5-dihydro-imidazo[4,5- c]pyridin-4-one

(94) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(pyrazolo[1,5-c]quinazolin-5-yl)methyl]-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

(95) 2-(3-amino-piperidin-1-yl)-3-(2-butyn-1-yl)-5-[(1H-perimidin-2-yl)methyl]-3,5-dihydro- imidazo[4,5-d]pyridazin-4-one

EXAMPLE 2 Coated Tablets Containing 75 mg of Active Substance

1 tablet core contains: active substance 75.0 mg calcium phosphate 93.0mg corn starch 35.5 mg polyvinylpyrrolidone 10.0 mghydroxypropylmethylcellulose 15.0 mg magnesium stearate  1.5 mg 230.0mg 

Preparation:

The active substance is mixed with calcium phosphate, corn starch,polyvinylpyrrolidone, hydroxypropylmethylcellulose and half thespecified amount of magnesium stearate. Blanks 13 mm in diameter areproduced in a tablet-making machine and these are then rubbed through ascreen with a mesh size of 1.5 mm using a suitable machine and mixedwith the rest of the magnesium stearate. This granulate is compressed ina tablet-making machine to form tablets of the desired shape.

-   -   Weight of core: 230 mg    -   die: 9 mm, convex

The tablet cores thus produced are coated with a film consistingessentially of hydroxypropylmethylcellulose. The finished film-coatedtablets are polished with beeswax.

-   -   Weight of coated tablet: 245 mg.

EXAMPLE 3 Tablets containing 100 mg of active substance

Composition: 1 tablet contains: active substance 100.0 mg lactose 80.0mg corn starch 34.0 mg polyvinylpyrrolidone 4.0 mg magnesium stearate2.0 mg 220.0 mg

Method of Preparation:

The active substance, lactose and starch are mixed together anduniformly moistened with an aqueous solution of thepolyvinylpyrrolidone. After the moist composition has been screened (2.0mm mesh size) and dried in a rack-type drier at 50° C. it is screenedagain (1.5 mm mesh size) and the lubricant is added. The finishedmixture is compressed to form tablets.

-   -   Weight of tablet: 220 mg    -   Diameter: 10 mm, biplanar, facetted on both sides and notched on        one side.

EXAMPLE 4 Tablets Containing 150 mg of Active Substance

Composition: 1 tablet contains: active substance 150.0 mg  powderedlactose 89.0 mg corn starch 40.0 mg colloidal silica 10.0 mgpolyvinylpyrrolidone 10.0 mg magnesium stearate  1.0 mg 300.0 mg 

Preparation:

The active substance mixed with lactose, corn starch and silica ismoistened with a 20% aqueous polyvinylpyrrolidone solution and passedthrough a screen with a mesh size of 1.5 mm. The granules, dried at 45°C., are passed through the same screen again and mixed with thespecified amount of magnesium stearate. Tablets are pressed from themixture.

-   -   Weight of tablet: 300 mg    -   die: 10 mm, flat

EXAMPLE 5 Hard Gelatine Capsules Containing 150 mg of Active Substance

1 capsule contains: active substance 150.0 mg corn starch (dried)approx. 80.0 mg lactose (powdered) approx. 87.0 mg magnesium stearate3.0 mg approx. 420.0 mg

Preparation:

The active substance is mixed with the excipients, passed through ascreen with a mesh size of 0.75 mm and homogeneously mixed using asuitable apparatus. The finished mixture is packed into size 1 hardgelatine capsules.

-   -   Capsule filling: approx. 320 mg    -   Capsule shell: size 1 hard gelatine capsule.

EXAMPLE 6 Suppositories Containing 150 mg of Active Substance

1 suppository contains: active substance 150.0 mg polyethyleneglycol1500 550.0 mg polyethyleneglycol 6000 460.0 mg polyoxyethylene sorbitanmonostearate 840.0 mg 2,000.0 mg 

Preparation:

After the suppository mass has been melted the active substance ishomogeneously distributed therein and the melt is poured into chilledmoulds.

EXAMPLE 7 Suspension Containing 50 mg of Active Substance

100 ml of suspension contain: active substance 1.00 gcarboxymethylcellulose-Na-salt 0.10 g methyl p-hydroxybenzoate 0.05 gpropyl p-hydroxybenzoate 0.01 g glucose 10.00 g glycerol 5.00 g 70%sorbitol solution 20.00 g flavouring 0.30 g dist. water ad 100 ml

Preparation:

The distilled water is heated to 70° C. The methyl and propylp-hydroxybenzoates together with the glycerol and sodium salt ofcarboxymethylcellulose are dissolved therein with stirring. The solutionis cooled to ambient temperature and the active substance is added andhomogeneously dispersed therein with stirring. After the sugar, thesorbitol solution and the flavouring have been added and dissolved, thesuspension is evacuated with stirring to eliminate air.

-   -   5 ml of suspension contain 50 mg of active substance.

EXAMPLE 8 Ampoules Containing 10 mg Active Substance

Composition: active substance 10.0 mg 0.01 N hydrochloric acid q.s.double-distilled water ad 2.0 ml

Preparation:

The active substance is dissolved in the necessary amount of 0.01 N HCl,made isotonic with common salt, filtered sterile and transferred into 2ml ampoules.

EXAMPLE 9 Ampoules Containing 50 mg of Active Substance

Composition: active substance 50.0 mg 0.01 N hydrochloric acid q.s.double-distilled water ad 10.0 ml

Preparation:

The active substance is dissolved in the necessary amount of 0.01 N HCl,made isotonic with common salt, filtered sterile and transferred into 10ml ampoules.

1. A compound of formula (I)

wherein R¹ denotes a C₁₋₃-alkyl group substituted by a group R_(a),where R_(a) denotes a 3,4-dihydro-quinolinyl, 3,4-dihydro-isoquinolinyl,1,4-dihydro-quinazolinyl, 3,4-dihydro-quinazolinyl,1H-benzo[d][1,2]oxazinyl, 4H-benzo[e][1,3]oxazinyl,4H-benzo[d][1,3]oxazinyl or 2H-benzo[1,4]oxazinyl group, wherein in eachcase in the benzo moiety one to three methyne groups may each bereplaced by a nitrogen atom and in the heterocyclyl moiety a methylenegroup may be replaced by a carbonyl group, a 4H-benzo[e][1,3]thiazinyl,4H-benzo[d][1,3]thiazinyl or 2H-benzo[1,4]thiazinyl group wherein ineach case in the benzo moiety one to three methyne groups may each bereplaced by a nitrogen atom and in the heterocyclyl moiety a methylenegroup may be replaced by a carbonyl group and the sulphur atom may bereplaced by a sulphinyl or sulphonyl group, a2-oxo-2H-benzo[e][1,3]oxazinyl or 2,2-dioxo-1H-benzo[c][1,2]thiazinylgroup wherein in each case in the benzo moiety one to three methynegroups may each be replaced by a nitrogen atom, a2,3-dihydro-1H-benzo[e][1,4]diazepinyl,4,5-dihydro-3H-benzo[b][1,4]diazepinyl or5-oxo-4,5-dihydro-3H-benzo[e][1,4]diazepinyl group wherein in each casein the benzo moiety one to three methyne groups may each be replaced bya nitrogen atom and in the heterocyclyl moiety a methylene group may bereplaced by a carbonyl group, a 2,3-dihydro-benzo[f][1,4]oxazepinyl or2,3-dihydro-benzo[b][1,4]oxazepinyl group wherein in each case in thebenzo moiety one to three methyne groups may each be replaced by anitrogen atom and in the heterocyclyl moiety a methylene group may bereplaced by a carbonyl group, a 2,3-dihydro-benzo[b][1,4]thiazepinyl or2,3-dihydro-benzo[f][1,4]thiazepinyl group wherein in each case in thebenzo moiety one to three methyne groups may each be replaced by anitrogen atom and in the heterocyclyl moiety a methylene group may bereplaced by a carbonyl group and the sulphur atom may be replaced by asulphinyl or sulphonyl group, a5-oxo-4,5-dihydro-benzo[f][1,3,4]oxadiazepinyl group wherein in thebenzo moiety one to three methyne groups may each be replaced by anitrogen atom, a 11H-dibenzo[b,e]azepinyl or5H-dibenzo[a,d]cycloheptenyl group wherein in each case in the benzomoiety one to three methyne groups may each be replaced by a nitrogenatom and the methylene group in the heterocyclyl moiety may be replacedby an oxygen or sulphur atom, a carbonyl, sulphinyl or sulphonyl groupor by an imino group substituted by R_(x), where R_(x) denotes ahydrogen atom or a C₁₋₄-alkyl, C₂₋₄-alkenyl, C₂₋₄-alkynyl,C₃₋₆-cycloalkyl, C₃₋₆-cycloalkyl-C₁₋₃-alkyl, aryl, aryl-C₁₋₃-alkyl,hydroxy-C₂₋₄-alkyl, C₁₋₃-alkyloxy-C₂₋₄-alkyl,C₃₋₆-cycloalkyloxy-C₂₋₄-alkyl, amino-C₂₋₄-alkyl,C₁₋₃-alkylamino-C₂₋₄-alkyl, di-(C₁₋₃-alkyl)-amino-C₂₋₄-alkyl,C₁₋₃-alkyl-carbonyl, C₁₋₃-alkyloxy-carbonyl,C₁₋₃-alkyloxy-carbonyl-C₁₋₃-alkyl, aryl-carbonyl, C₁₋₃-alkyl-sulphonylor aryl-sulphonyl group, a phenanthridinyl group wherein in the benzomoiety one to three methyne groups may each be replaced by a nitrogenatom, and a 1,2,3,4-tetrahydro-phenanthridinyl,1,2,3,4,4a,10b-hexahydro-phenanthridinyl,2,3-dihydro-1H-4-aza-cyclopenta[a]naphthyl or a8,9,10,11-tetrahydro-7H-6-aza-cyclohepta[a]naphthyl group wherein ineach case in the benzo moiety one to three methyne groups may each bereplaced by a nitrogen atom and one or two methylene groups may each bereplaced by an oxygen atom or a carbonyl group, while, if two methylenegroups are each replaced by an oxygen atom, the oxygen atoms must beseparated from one another by at least two methylene units, aphenanthrenyl group wherein in each case one to three of the methynegroups in position 1 to 4 and 5 to 8 may each be replaced by a nitrogenatom, a 1,2,3,4-tetrahydro-phenanthrenyl or a1,2,3,4,5,6,7,8-octahydro-phenanthrenyl group wherein in each case oneor two of the methylene groups in position 1 to 4 and 5 to 8 may each bereplaced by an oxygen atom or a carbonyl group, while, if two methylenegroups are each replaced by an oxygen atom, the oxygen atoms must beseparated from one another by at least two methylene units, a5H-benzo[e]pyrrolo[1,2-a][1,4]diazepinyl,thieno[3,2-b][1,4]benzoxazepinyl, 5H-dibenzo[d,f][1,3]diazepinyl or a5-oxa-7-aza-dibenzo[a,c]cycloheptenyl group wherein in each case in thebenzo moiety one to three methyne groups may each be replaced by anitrogen atom, a naphtho[1,2-d]oxazolyl, naphtho[2,1-d]oxazolyl,naphtho[1,2-d]thiazolyl, naphtho[2,1-d]thiazolyl,naphtho[1,2-d]imidazolyl, naphtho[1,2-b]furanyl or naphtho[2,1-b]furanylgroup wherein in each case in the naphthyl moiety one to three methynegroups may each be replaced by a nitrogen atom, or afuro[3,2-c]isoquinolinyl, pyrazolo[1,5-c]quinazolinyl or 1H-perimidinylgroup, while the methylene and methyne groups of the above mentionedradicals R_(a) may be substituted by the groups R¹⁰ to R¹³ andadditionally by a C₁₋₃-alkyl group and the imino groups of the abovementioned radicals R_(a) may be substituted by the groups R_(X), ashereinbefore defined and R¹⁰ denotes a hydrogen atom, a fluorine,chlorine, bromine or iodine atom, a C₁₋₄-alkyl, hydroxy, orC₁₋₄-alkyloxy group, a nitro, amino, C₁₋₃-alkylamino,di-(C₁₋₃-alkyl)amino, cyano-C₁₋₃-alkylamino,N-(cyano-C₁₋₃-alkyl)-N—(C₁₋₃-alkyl)-amino,C₁₋₃-alkyloxy-carbonyl-C₁₋₃-alkylamino, pyrrolidin-1-yl, piperidin-1-yl,morpholin-4-yl, piperazin-1-yl, or 4-(C₁₋₃-alkyl)-piperazin-1-yl group,a C₁₋₃-alkyl-carbonylamino, arylcarbonylamino,aryl-C₁₋₃-alkyl-carbonylamino, C₁₋₃-alkyloxy-carbonylamino,aminocarbonylamino, C₁₋₃-alkylaminocarbonylamino,di-(C₁₋₃-alkyl)aminocarbonylamino, pyrrolidin-1-yl-carbonylamino,piperidin-1-yl-carbonylamino, morpholin-4-yl-carbonylamino,piperazin-1-yl-carbonylamino or4-(C₁₋₃-alkyl)-piperazin-1-yl-carbonylamino, C₁₋₃-alkyl-sulphonylamino,bis-(C₁₋₃-alkylsulphonyl)-amino, aminosulphonylamino,C₁₋₃-alkylamino-sulphonylamino, di-(C₁₋₃-alkyl)amino-sulphonylamino,pyrrolidin-1-yl-sulphonylamino, piperidin-1-yl-sulphonylamino,morpholin-4-yl-sulphonylamino, piperazin-1-yl-sulphonylamino or4-(C₁₋₃-alkyl)-piperazin-1-yl-sulphonylamino,(C₁₋₃-alkylamino)thiocarbonylamino,(C₁₋₃-alkyloxy-carbonyl-amino)carbonylamino, arylsulphonylamino oraryl-C₁₋₃-alkyl-sulphonyl-amino group, anN—(C₁₋₃-alkyl)-C₁₋₃-alkyl-carbonylamino,N—(C₁₋₃-alkyl)-arylcarbonylamino,N—(C₁₋₃-alkyl)-aryl-C₁₋₃-alkyl-carbonylamino,N—(C₁₋₃-alkyl)-C₁₋₃-alkyloxy-carbonylamino,N-(aminocarbonyl)-C₁₋₃-alkylamino,N—(C₁₋₃-alkyl-aminocarbonyl)-C₁₋₃-alkylamino,N-[di-(C₁₋₃-alkyl)aminocarbonyl]-C₁₋₃-alkylamino,N—(C₁₋₃-alkyl)-C₁₋₃-alkyl-sulphonylamino,N—(C₁₋₃-alkyl)-arylsulphonylamino, orN—(C₁₋₃-alkyl)-aryl-C₁₋₃-alkyl-sulphonylamino group, a2-oxo-imidazolidin-1-yl, 2,4-dioxo-imidazolidin-1-yl,2,5-dioxo-imidazolidin-1-yl or 2-oxo-hexahydropyrimidin-1-yl groupwherein the nitrogen atom in the 3 position may be substituted in eachcase by a methyl or ethyl group, a cyano, carboxy,C₁₋₃-alkyloxy-carbonyl, aminocarbonyl, C₁₋₃-alkyl-aminocarbonyl,di-(C₁₋₃-alkyl)-aminocarbonyl, pyrrolidin-1-yl-carbonyl,piperidin-1-yl-carbonyl, morpholin-4-yl-carbonyl,piperazin-1-yl-carbonyl or 4-(C₁₋₃-alkyl)-piperazin-1-yl-carbonyl group,a C₁₋₃-alkyl-carbonyl or an arylcarbonyl group, a carboxy-C₁₋₃-alkyl,C₁₋₃-alkyloxy-carbonyl-C₁₋₃-alkyl, cyano-C₁₋₃-alkyl,aminocarbonyl-C₁₋₃-alkyl, C₁₋₃-alkyl-aminocarbonyl-C₁₋₃-alkyl,di-(C₁₋₃-alkyl)-aminocarbonyl-C₁₋₃-alkyl,pyrrolidin-1-yl-carbonyl-C₁₋₃-alkyl, piperidin-1-yl-carbonyl-C₁₋₃-alkyl,morpholin-4-yl-carbonyl-C₁₋₃-alkyl, piperazin-1-yl-carbonyl-C₁₋₃-alkylor 4-(C₁₋₃-alkyl)-piperazin-1-yl-carbonyl-C₁₋₃-alkyl group, acarboxy-C₁₋₃-alkyloxy, C₁₋₃-alkyloxy-carbonyl-C₁₋₃-alkyloxy,cyano-C₁₋₃-alkyloxy, aminocarbonyl-C₁₋₃-alkyloxy,C₁₋₃-alkyl-aminocarbonyl-C₁₋₃-alkyloxy,di-(C₁₋₃-alkyl)-aminocarbonyl-C₁₋₃-alkyloxy,pyrrolidin-1-yl-carbonyl-C₁₋₃-alkyloxy,piperidin-1-yl-carbonyl-C₁₋₃-alkyloxy,morpholin-4-yl-carbonyl-C₁₋₃-alkyloxy,piperazin-1-yl-carbonyl-C₁₋₃-alkyloxy or4-(C₁₋₃-alkyl)-piperazin-1-yl-carbonyl-C₁₋₃-alkyloxy group, ahydroxy-C₁₋₃-alkyl, C₁₋₃-alkyloxy-C₁₋₃-alkyl, amino-C₁₋₃-alkyl,C₁₋₃-alkylamino-C₁₋₃-alkyl, di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl,pyrrolidin-1-yl-C₁₋₃-alkyl, piperidin-1-yl-C₁₋₃-alkyl,morpholin-4-yl-C₁₋₃-alkyl, piperazin-1-yl-C₁₋₃-alkyl or4-(C₁₋₃-alkyl)-piperazin-1-yl-C₁₋₃-alkyl group, a hydroxy-C₁₋₃-alkyloxy,C₁₋₃-alkyloxy-C₁₋₃-alkyloxy, C₁₋₃-alkylsulphanyl-C₁₋₃-alkyloxy,C₁₋₃-alkylsulphinyl-C₁₋₃-alkyloxy, C₁₋₃-alkylsulphonyl-C₁₋₃-alkyloxy,amino-C₁₋₃-alkyloxy, C₁₋₃-alkylamino-C₁₋₃-alkyloxy,di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyloxy, pyrrolidin-1-yl-C₁₋₃-alkyloxy,piperidin-1-yl-C₁₋₃-alkyloxy, morpholin-4-yl-C₁₋₃-alkyloxy,piperazin-1-yl-C₁₋₃-alkyloxy or4-(C₁₋₃-alkyl)-piperazin-1-yl-C₁₋₃-alkyloxy group, a mercapto,C₁₋₃-alkylsulphanyl, C₁₋₃-alkysulphinyl, C₁₋₃-alkylsulphonyl,C₁₋₃-alkylsulphonyloxy, arylsulphonyloxy, trifluoromethylsulphanyl,trifluoromethylsulphinyl or trifluoromethylsulphonyl group, a sulpho,aminosulphonyl, C₁₋₃-alkyl-aminosulphonyl,di-(C₁₋₃-alkyl)-aminosulphonyl, pyrrolidin-1-yl-sulphonyl,piperidin-1-yl-sulphonyl, morpholin-4-yl-sulphonyl,piperazin-1-yl-sulphonyl or 4-(C₁₋₃-alkyl)-piperazin-1-yl-sulphonylgroup, a methyl or methoxy group substituted by 1 to 3 fluorine atoms,an ethyl or ethoxy group substituted by 1 to 5 fluorine atoms, aC₂₋₄-alkenyl or C₂₋₄-alkynyl group, a C₃₋₄-alkenyloxy or C₃₋₄-alkynyloxygroup, a C₃₋₆-cycloalkyl or C₃₋₆-cycloalkyloxy group, aC₃₋₆-cycloalkyl-C₁₋₃-alkyl or C₃₋₆-cycloalkyl-C₁₋₃-alkyloxy group or anaryl, aryloxy, aryl-C₁₋₃-alkyl or aryl-C₁₋₃-alkyloxy group, R¹¹ and R¹²,which may be identical or different, in each case represent a hydrogenatom, a fluorine, chlorine, bromine or iodine atom, a C₁₋₃-alkyl,trifluoromethyl, hydroxy, C₁₋₃-alkyloxy or cyano group, or R¹¹ togetherwith R¹², if these are bound to adjacent carbon atoms, also denotes amethylenedioxy, difluoromethylenedioxy, ethylenedioxy or astraight-chain C₃₋₅-alkylene group and R¹³ denotes a hydrogen atom, afluorine, chlorine or bromine atom, a trifluoromethyl, C₁₋₃-alkyl orC₁₋₃-alkyloxy group, R² denotes a hydrogen, fluorine or chlorine atom, aC₁₋₆-alkyl group, a C₂₋₄-alkenyl group, a C₃₋₄-alkynyl group, aC₃₋₆-cycloalkyl group, a C₃₋₆-cycloalkyl-C₁₋₃-alkyl group, atetrahydrofuran-3-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl,tetrahydrofuranylmethyl or tetrahydropyranylmethyl group, an aryl group,an aryl-C₁₋₄-alkyl group, an aryl-C₂₋₃-alkenyl group, an arylcarbonylgroup, an arylcarbonyl-C₁₋₂-alkyl group, a heteroaryl group, aheteroaryl-C₁₋₃-alkyl group, a furanylcarbonyl, thienylcarbonyl,thiazolylcarbonyl or pyridylcarbonyl group, a furanylcarbonylmethyl,thienylcarbonylmethyl, thiazolylcarbonylmethyl or pyridylcarbonylmethylgroup, a C₁₋₄-alkyl-carbonyl group, a C₁₋₄-alkyl-carbonyl-C₁₋₂-alkylgroup, a C₃₋₆-cycloalkyl-carbonyl group, aC₃₋₆-cycloalkyl-carbonyl-C₁₋₂-alkyl group, an aryl-A oraryl-A-C₁₋₃-alkyl group, where A denotes an oxygen or sulphur atom, animino, C₁₋₃-alkylimino, sulphinyl or sulphonyl group, a group R_(b),where R_(b) denotes a cyano, carboxy, C₁₋₃-alkyloxy-carbonyl,aminocarbonyl, C₁₋₃-alkyl-amino-carbonyl,di-(C₁₋₃-alkyl)-amino-carbonyl, pyrrolidin-1-ylcarbonyl,piperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl, piperazin-1-ylcarbonyl,4-methylpiperazin-1-ylcarbonyl, 4-ethylpiperazin-1-ylcarbonyl, hydroxy,mercapto, C₁₋₃-alkyloxy, C₁₋₃-alkylsulphenyl, C₁₋₃-alkylsulphinyl,C₁₋₃-alkylsulphonyl, amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino,pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl, piperazin-1-yl,4-methyl-piperazin-1-yl or 4-ethyl-piperazin-1-yl group, or a C₁₋₄-alkylgroup substituted by a group R_(b), where R_(b) is as hereinbeforedefined, Y denotes a group of formula C—R⁵, while R⁵ is defined like R²and in each case one of the two groups R² and R⁵ must be a hydrogen atomor a C₁₋₃-alkyl group, R³ denotes a C₃₋₈-alkyl group, a C₁₋₃-alkyl groupsubstituted by a group R_(c), where R_(c), denotes a C₃₋₇-cycloalkylgroup optionally substituted by one or two C₁₋₃-alkyl groups, aC₅₋₇-cycloalkenyl group optionally substituted by one or two C₁₋₃-alkylgroups, an aryl group or a furanyl, thienyl, oxazolyl, isoxazolyl,thiazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrimidyl or pyrazinylgroup, while the above mentioned heterocyclic groups may each besubstituted by one or two C₁₋₃-alkyl groups or by a fluorine, chlorine,bromine or iodine atom or by a trifluoromethyl, cyano or C₁₋₃-alkyloxygroup, a C₃₋₈-alkenyl group, a C₃₋₆-alkenyl group substituted by afluorine, chlorine or bromine atom or by a trifluoromethyl group, aC₃₋₈-alkynyl group, an aryl group or an aryl-C₂₋₄-alkenyl group, and R⁴denotes an azetidin-1-yl or pyrrolidin-1-yl group which is substitutedin the 3 position by an amino, C₁₋₃-alkylamino or a di-(C₁₋₃-alkyl)aminogroup and may additionally be substituted by one or two C₁₋₃-alkylgroups, a piperidin-1-yl or hexahydroazepin-1-yl group which issubstituted in the 3 position or in the 4 position by an amino,C₁₋₃-alkylamino or a di-(C₁₋₃-alkyl)amino group and may additionally besubstituted by one or two C₁₋₃-alkyl groups, a 3-amino-piperidin-1-ylgroup wherein the piperidin-1-yl-moiety is additionally substituted byan aminocarbonyl, C₁₋₂-alkyl-aminocarbonyl,di-(C₁₋₂-alkyl)aminocarbonyl, pyrrolidin-1-yl-carbonyl,(2-cyano-pyrrolidin-1-yl-)carbonyl, thiazolidin-3-yl-carbonyl,(4-cyano-thiazolidin-3-yl)carbonyl, piperidin-1-ylcarbonyl ormorpholin-4-ylcarbonyl group, a 3-amino-piperidin-1-yl group wherein thepiperidin-1-yl moiety in the 4 position or in the position isadditionally substituted by a hydroxy or methoxy group, a3-amino-piperidin-1-yl group wherein the methylene group in the 2position or in the 6 position is replaced by a carbonyl group, apiperidin-1-yl or hexahydroazepin-1-yl group substituted in the 3position by an amino, C₁₋₃-alkylamino or di-(C₁₋₃-alkyl)-amino-group,wherein in each case two hydrogen atoms on the carbon skeleton of thepiperidin-1-yl or hexahydroazepin-1-yl-group are replaced by astraight-chain alkylene bridge, this bridge containing 2 to 5 carbonatoms if the two hydrogen atoms are located on the same carbon atom, or1 to 4 carbon atoms, if the hydrogen atoms are located on adjacentcarbon atoms, or 1 to 4 carbon atoms, if the hydrogen atoms are locatedon carbon atoms which are separated by one atom, or 1 to 3 carbon atomsif the two hydrogen atoms are located on carbon atoms separated by twoatoms, an azetidin-1-yl, pyrrolidin-1-yl, piperidin-1-yl orhexahydroazepin-1-yl group which is substituted by an amino-C₁₋₃-alkyl,C₁₋₃-alkylamino-C₁₋₃-alkyl or a di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl group,a piperazin-1-yl or [1,4]diazepan-1-yl group optionally substituted atthe carbon skeleton by one or two C₁₋₃-alkyl groups, a3-imino-piperazin-1-yl, 3-imino-[1,4]diazepan-1-yl or5-imino-[1,4]diazepan-1-yl group optionally substituted at the carbonskeleton by one or two C₁₋₃-alkyl groups, a [1,4]diazepan-1-yl groupoptionally substituted by one or two C₁₋₃-alkyl groups, which issubstituted in the 6 position by an amino group, a C₃₋₇-cycloalkyl groupwhich is substituted by an amino, C₁₋₃-alkylamino ordi-(C₁₋₃-alkyl)-amino group, a C₃₋₇-cycloalkyl group which issubstituted by an amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl or adi-(C₁₋₃-alkyl)amino-C₁₋₃-alkyl group, a C₃₋₇-cycloalkyl-C₁₋₂-alkylgroup wherein the cycloalkyl moiety is substituted by an amino,C₁₋₃-alkylamino or di-(C₁₋₃-alkyl)-amino group, aC₃₋₇-cycloalkyl-C₁₋₂-alkyl group wherein the cycloalkyl moiety issubstituted by an amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl or adi-(C₁₋₃-alkyl)amino-C₁₋₃-alkyl group, a C₃₋₇-cycloalkylamino groupwherein the cycloalkyl moiety is substituted by an amino,C₁₋₃-alkylamino or di-(C₁₋₃-alkyl)-amino group, while the two nitrogenatoms at the cycloalkyl moiety are separated from one another by atleast two carbon atoms, an N—(C₃₋₇-cycloalkyl)-N—(C₁₋₃-alkyl)-aminogroup wherein the cycloalkyl moiety is substituted by an amino,C₁₋₃-alkylamino or di-(C₁₋₃-alkyl)-amino group, while the two nitrogenatoms at the cycloalkyl moiety are separated from one another by atleast two carbon atoms, a C₃₋₇-cycloalkylamino group wherein thecycloalkyl moiety is substituted by an amino-C₁₋₃-alkyl,C₁₋₃-alkylamino-C₁₋₃-alkyl or a di-(C₁₋₃-alkyl)amino-C₁₋₃-alkyl group,an N—(C₃₋₇-cycloalkyl)-N—(C₁₋₃-alkyl)-amino group wherein the cycloalkylmoiety is substituted by an amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkylor a di-(C₁₋₃-alkyl)amino-C₁₋₃-alkyl group, aC₃₋₇-cycloalkyl-C₁₋₂-alkyl-amino group wherein the cycloalkyl moiety issubstituted by an amino, C₁₋₃-alkylamino or di-(C₁₋₃-alkyl)-amino group,an N—(C₃₋₇-cycloalkyl-C₁₋₂-alkyl)-N—(C₁₋₂-alkyl)-amino group wherein thecycloalkyl moiety is substituted by an amino, C₁₋₃-alkylamino ordi-(C₁₋₃-alkyl)-amino group, a C₃₋₇-cycloalkyl-C₁₋₂-alkyl-amino groupwherein the cycloalkyl moiety is substituted by an amino-C₁₋₃-alkyl,C₁₋₃-alkylamino-C₁₋₃-alkyl or a di-(C₁₋₃-alkyl)amino-C₁₋₃-alkyl group,an N—(C₃₋₇-cycloalkyl-C₁₋₂-alkyl)-N—(C₁₋₂-alkyl)-amino group wherein thecycloalkyl moiety is substituted by an amino-C₁₋₃-alkyl,C₁₋₃-alkylamino-C₁₋₃-alkyl or a di-(C₁₋₃-alkyl)amino-C₁₋₃-alkyl group, aR¹⁹—C₂₋₄-alkylamino group wherein R¹⁹ is separated from the nitrogenatom of the C₂₋₄-alkylamino moiety by at least two carbon atoms and R¹⁹denotes an amino, C₁₋₃-alkylamino or di-(C₁₋₃-alkyl)-amino group, anR¹⁹—C₂₋₄-alkylamino group wherein the nitrogen atom of theC₂₋₄-alkylamino moiety is substituted by a C₁₋₃-alkyl group and R¹⁹ isseparated from the nitrogen atom of the C₂₋₄-alkylamino moiety by atleast two carbon atoms, while R¹⁹ is as hereinbefore defined, an aminogroup substituted by the group R²⁰ wherein R²⁰ denotes an azetidin-3-yl,azetidin-2-ylmethyl, azetidin-3-ylmethyl, pyrrolidin-3-yl,pyrrolidin-2-ylmethyl, pyrrolidin-3-ylmethyl, piperidin-3-yl,piperidin-4-yl, piperidin-2-ylmethyl, piperidin-3-ylmethyl orpiperidin-4-ylmethyl group, while the groups mentioned for R²⁰ may eachbe substituted by one or two C₁₋₃-alkyl groups, an amino groupsubstituted by the group R²⁰ and a C₁₋₃-alkyl group wherein R²⁰ is ashereinbefore defined, while the groups mentioned for R²⁰ may each besubstituted by one or two C₁₋₃-alkyl groups, an R¹⁹—C₃₋₄-alkyl groupwherein the C₃₋₄-alkyl moiety is straight-chained and may additionallybe substituted by one or two C₁₋₃-alkyl groups, while R¹⁹ is ashereinbefore defined, a 3-amino-2-oxo-piperidin-5-yl or3-amino-2-oxo-1-methyl-piperidin-5-yl group, a pyrrolidin-3-yl,piperidin-3-yl, piperidin-4-yl, hexahydroazepin-3-yl orhexahydroazepin-4-yl group which is substituted in the 1 position by anamino, C₁₋₃-alkylamino or di-(C₁₋₃-alkyl)amino group, or anazetidin-2-yl-C₁₋₂-alkyl, azetidin-3-yl-C₁₋₂-alkyl,pyrrolidin-2-yl-C₁₋₂-alkyl, pyrrolidin-3-yl, pyrrolidin-3-yl-C₁₋₂-alkyl,piperidin-2-yl-C₁₋₂-alkyl, piperidin-3-yl, piperidin-3-yl-C₁₋₂-alkyl,piperidin-4-yl or piperidin-4-yl-C₁₋₂-alkyl group, while the abovementioned groups may each be substituted by one or two C₁₋₃-alkylgroups, while by the aryl groups mentioned in the definition of theabove groups are meant phenyl or naphthyl groups which may be mono- ordisubstituted by R_(h), while the substituents may be identical ordifferent and R_(h) denotes a fluorine, chlorine, bromine or iodineatom, a trifluoromethyl, cyano, nitro, amino, aminocarbonyl,aminosulphonyl, methylsulphonyl, acetylamino, methylsulphonylamino,C₁₋₃-alkyl, cyclopropyl, ethenyl, ethynyl, hydroxy, C₁₋₃-alkyloxy,difluoromethoxy or trifluoromethoxy group, by the heteroaryl groupsmentioned in the definition of the above groups are meant a pyrrolyl,furanyl, thienyl, pyridyl, indolyl, benzofuranyl, benzothiophenyl,quinolinyl or isoquinolinyl group, or a pyrrolyl, furanyl, thienyl orpyridyl group, wherein one or two methyne groups are replaced bynitrogen atoms, or an indolyl, benzofuranyl, benzothiophenyl, quinolinylor isoquinolinyl group, wherein one to three methyne groups are replacedby nitrogen atoms, and the above mentioned heteroaryl groups may bemono- or disubstituted by R_(h), while the substituents may be identicalor different and R_(h) is as hereinbefore defined, while, unlessotherwise stated, the above mentioned alkyl, alkenyl and alkynyl groupsmay be straight-chain or branched, and the hydrogen atoms of the methylor ethyl groups contained in the definitions may be wholly or partlyreplaced by fluorine atoms, or a tautomer, enantiomer, diastereomer,mixture thereof, prodrug thereof or salt thereof.
 2. The compound offormula I according to claim 1, wherein R¹ denotes a methyl groupsubstituted by a group R_(a), where R_(a) denotes a3,4-dihydro-quinolinyl group, a 3,4-dihydro-isoquinolinyl group, a1,4-dihydro-quinazolinyl or 4-oxo-1,4-dihydro-quinazolinyl group, a3,4-dihydro-quinazolinyl or 4-oxo-3,4-dihydro-quinazolinyl group, a1H-benzo[d][1,2]oxazinyl or 1-oxo-1H-benzo[d][1,2]oxazinyl group, a4H-benzo[e][1,3]oxazinyl or 4-oxo-4H-benzo[e][1,3]oxazinyl group, a4H-benzo[d][1,3]oxazinyl or 4-oxo-4H-benzo[d][1,3]oxazinyl group, a2H-benzo[1,4]oxazinyl or 2-oxo-2H-benzo[1,4]oxazinyl group, a4H-benzo[e][1,3]thiazinyl or 4-oxo-4H-benzo[e][1,3]thiazinyl group, a4H-benzo[d][1,3]thiazinyl or 2H-benzo[1,4]thiazinyl group, a2-oxo-2H-benzo[e][1,3]oxazinyl or 2,2-dioxo-1H-benzo[c][1,2]thiazinylgroup, a 2,3-dihydro-1H-benzo[e][1,4]diazepinyl or2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepinyl group, a4,5-dihydro-3H-benzo[b][1,4]diazepinyl or4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepinyl group, a5-oxo-4,5-dihydro-3H-benzo[e][1,4]diazepinyl group, a2,3-dihydro-benzo[f][1,4]oxazepinyl or2,3-dihydro-benzo[b][1,4]oxazepinyl group, a2,3-dihydro-benzo[f][1,4]thiazepinyl or2,3-dihydro-benzo[b][1,4]thiazepinyl group, a5-oxo-4,5-dihydro-benzo[f][1,3,4]oxadiazepinyl group, a11H-dibenzo[b,e]azepinyl or 11-oxo-11H-dibenzo[b,e]azepinyl group, a11H-benzo[e]pyrido[3,2-b]azepinyl or a5H-1,9,10-triaza-dibenzo[a,d]-cycloheptenyl group, a5H-dibenzo[b,e][1,4]diazepinyl or dibenzo[b,f][1,4]oxazepinyl group, adibenzo[b,f][1,4]thiazepinyl, 5-oxo-dibenzo[b,f][1,4]thiazepinyl or5,5-dioxo-dibenzo[b,f][1,4]thiazepinyl group, a5H-dibenzo[a,d]cycloheptenyl or 5H-dibenzo[b,f]azepinyl group, aphenanthridinyl, benzo[c][1,5]naphthyridinyl,benzo[h][1,6]naphthyridinyl, benzo[c][1,8]naphthyridinyl,benzo[f][1,7]naphthyridinyl or 1,5,9-triaza-phenanthrenyl group, a1,2,3,4-tetrahydro-phenanthridinyl,1,2,3,4,4a,10b-hexahydro-phenanthridinyl,2,3-dihydro-1H-4-aza-cyclopenta[a]naphthyl or8,9,10,11-tetrahydro-7H-6-aza-cyclohepta[a]naphthyl group, a2,3-dihydro-1H-4-oxa-10-aza-phenanthrenyl or1-oxo-2,3-dihydro-1H-4-oxa-10-aza-phenanthrenyl group, a phenanthrenyl,benzo[h]quinolinyl, benzo[f]quinolinyl or benzo[f]quinoxalinyl group, a5H-benzo[e]pyrrolo[1,2-a][1,4]diazepinyl,thieno[3,2-b][1,4]benzoxazepinyl, 5H-dibenzo[d,f][1,3]diazepinyl or5-oxa-7-aza-dibenzo[a,c]cycloheptenyl group, a naphtho[1,2-d]oxazolyl,naphtho[2,1-d]oxazolyl, naphtho[1,2-d]thiazolyl,naphtho[2,1-d]thiazolyl, naphtho[1,2-d]imidazolyl, naphtho[1,2-b]furanylor naphtho[2,1-b]furanyl group, or a furo[3,2-c]isoquinolinyl,pyrazolo[1,5-c]quinazolinyl or 1H-perimidinyl group, while the benzogroups of the above mentioned radicals R_(a) are substituted by thegroups R¹⁰ to R¹³ and the alkylene units of the above mentioned groupsR_(a) may be substituted by one or two fluorine atoms or one or twoC₁₋₃-alkyl or C₁₋₃-alkyloxy-carbonyl groups and the imino groups of theabove mentioned radicals R_(a) may be substituted by a C₁₋₃-alkyl groupand R¹⁰ denotes a hydrogen atom, a fluorine, chlorine, bromine or iodineatom, a C₁₋₃-alkyl or cyclopropyl group, a hydroxy, C₁₋₃-alkyloxy orcyclopropyloxy group, a nitro, amino, C₁₋₃-alkylamino ordi-(C₁₋₃-alkyl)amino group, a C₁₋₃-alkyl-carbonylamino orC₁₋₃-alkyl-sulphonylamino group, a cyano, carboxy,C₁₋₃-alkyloxy-carbonyl, aminocarbonyl, C₁₋₃-alkyl-aminocarbonyl ordi-(C₁₋₃-alkyl)-aminocarbonyl group, a mercapto, C₁₋₃-alkylsulphanyl,C₁₋₃-alkysulphinyl, C₁₋₃-alkylsulphonyl or aminosulphonyl group or adifluoromethyl, trifluoromethyl, difluoromethoxy or trifluoromethoxygroup and R¹¹, R¹² and R¹³, which may be identical or different, in eachcase represent a hydrogen atom, a fluorine, chlorine or bromine atom, amethyl, trifluoromethyl or methoxy group, R² denotes a hydrogen atom ora C₁₋₃-alkyl, cyclopropyl, trifluoromethyl, cyanomethyl or 2-cyano-ethylgroup, Y denotes a group of formula C—R⁵, while R⁵ denotes a hydrogenatom or a C₁₋₃-alkyl group, R³ denotes a 2-buten-1-yl or3-methyl-2-buten-1-yl group, a 1-buten-1-yl group, a 2-butyn-1-yl groupor a 1-cyclopenten-1-ylmethyl group and R⁴ denotes a(3-amino-piperidin-1-yl) group, while, unless otherwise stated, theabove mentioned alkyl groups may be straight-chain or branched, or atautomer, enantiomer, diastereomer, mixture thereof, or salt thereof. 3.The compound of formula I according to claim 2, wherein R¹ denotes amethyl group substituted by a group R_(a), where R_(a) denotes a3,4-dihydro-quinolin-2-yl group, a 3,4-dihydro-isoquinolin-1-yl group, a1,4-dihydro-quinazolin-2-yl or 4-oxo-1,4-dihydro-quinazolin-2-yl group,a 3,4-dihydro-quinazolin-2-yl or 4-oxo-3,4-dihydro-quinazolin-2-ylgroup, a 1H-benzo[d][1,2]oxazin-4-yl or1-oxo-1H-benzo[d][1,2]oxazin-4-yl group, a 4H-benzo[e][1,3]oxazin-2-ylor 4-oxo-4H-benzo[e][1,3]oxazin-2-yl group, a4H-benzo[d][1,3]oxazin-2-yl or 4-oxo-4H-benzo[d][1,3]oxazin-2-yl group,a 2H-benzo[1,4]oxazin-3-yl or 2-oxo-2H-benzo[1,4]oxazin-3-yl group, a4H-benzo[e][1,3]thiazin-2-yl or 4-oxo-4H-benzo[e][1,3]thiazin-2-ylgroup, a 4H-benzo[d][1,3]thiazin-2-yl or 2H-benzo[1,4]thiazin-3-ylgroup, a 2-oxo-2H-benzo[e][1,3]oxazin-4-yl or2,2-dioxo-1H-benzo[c][1,2]thiazin-4-yl group, a2,3-dihydro-1H-benzo[e][1,4]diazepin-5-yl or2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-5-yl group, a4,5-dihydro-3H-benzo[b]h[1,4]diazepin-2-yl or4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl group, a5-oxo-4,5-dihydro-3H-benzo[e][1,4]diazepin-2-yl group, a2,3-dihydro-benzo[f][1,4]oxazepin-5-yl or2,3-dihydro-benzo[b][1,4]oxazepin-4-yl group, a2,3-dihydro-benzo[f][1,4]thiazepin-5-yl or2,3-dihydro-benzo[b][1,4]thiazepin-4-yl group, a5-oxo-4,5-dihydro-benzo[f][1,3,4]oxadiazepin-2-yl group, a11H-dibenzo[b,e]azepin-6-yl or 11-oxo-11H-dibenzo[b,e]azepin-6-yl group,a 11H-benzo[e]pyrido[3,2-b]azepin-6-yl or a5H-1,9,10-triaza-dibenzo[a,d]-cyclohepten-11-yl group, a5H-dibenzo[b,e][1,4]diazepin-11-yl or dibenzo[b,f][1,4]oxazepin-11-ylgroup, a dibenzo[b,f][1,4]thiazepin-11-yl,5-oxo-dibenzo[b,f][1,4]thiazepin-11-yl or5,5-dioxo-dibenzo[b,f][1,4]thiazepin-11-yl group, a5H-dibenzo[a,d]cyclohepten-10-yl or 5H-dibenzo[b,f]azepin-10-yl group, aphenanthridin-6-yl, benzo[c][1,5]naphthyridin-6-yl,benzo[h][1,6]naphthyridin-5-yl, benzo[c][1,8]naphthyridin-6-yl,benzo[f][1,7]naphthyridin-5-yl or 1,5,9-triaza-phenanthren-10-yl group,a 1,2,3,4-tetrahydro-phenanthridin-6-yl,1,2,3,4,4a,10b-hexahydro-phenanthridin-6-yl,2,3-dihydro-1H-4-aza-cyclopenta[a]naphth-5-yl or8,9,10,11-tetrahydro-7H-6-aza-cyclohepta[a]naphth-5-yl group, a2,3-dihydro-1H-4-oxa-10-aza-phenanthren-9-yl or1-oxo-2,3-dihydro-1H-4-oxa-10-aza-phenanthren-9-yl group, aphenanthren-9-yl, benzo[h]quinolin-6-yl, benzo[f]quinolin-6-yl orbenzo[f]quinoxalin-6-yl group, a5H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-11-yl,thieno[3,2-b][1,4]benzoxazepin-9-yl, 5H-dibenzo[d,f][1,3]diazepin-6-ylor 5-oxa-7-aza-dibenzo[a,c]cyclohepten-6-yl group, anaphtho[1,2-d]oxazol-2-yl, naphtho[2,1-d]oxazol-2-yl,naphtho[1,2-d]thiazol-2-yl, naphtho[2,1-d]thiazol-2-yl,naphtho[1,2-d]imidazol-2-yl, naphtho[1,2-b]furan-2-yl ornaphtho[2,1-b]furan-2-yl group, or a furo[3,2-c]isoquinolin-5-yl,pyrazolo[1,5-c]quinazolin-5-yl or 1H-perimidin-2-yl group, while thebenzo groups of the above mentioned radicals R_(a) are substituted bythe groups R¹⁰ to R¹³ and the alkylene units of the above mentionedgroups R_(a) may be substituted by one or two fluorine atoms or one ortwo methyl groups and the imino groups of the above mentioned radicalsR_(a) may be substituted by a methyl group and R¹⁰ denotes a hydrogenatom, a fluorine, chlorine, bromine or iodine atom, a methyl or ethylgroup, a hydroxy, methoxy or ethoxy group or a difluoromethyl,trifluoromethyl, difluoromethoxy, or trifluoromethoxy group and R¹¹, R¹²and R¹³, which may be identical or different, each denote a hydrogen,fluorine, chlorine or bromine atom or a methyl, trifluoromethyl ormethoxy group, R² denotes a hydrogen atom or a methyl, cyanomethyl,trifluoromethyl, ethyl, 2-cyano-ethyl, propyl, cyclopropyl or isopropylgroup, Y denotes a group of formula C—R⁵, while R⁵ denotes a hydrogenatom or a methyl, ethyl, propyl or isopropyl group, R³ denotes a2-buten-1-yl or 3-methyl-2-buten-1-yl group, a 1-buten-1-yl group, a2-butyn-1-yl group or a 1-cyclopenten-1-ylmethyl group and R⁴ denotes a(3-amino-piperidin-1-yl) group, or a tautomer, enantiomer, diastereomer,mixture thereof, or salt thereof.
 4. (canceled)
 5. (canceled)
 6. Aphysiologically acceptable salt of the compound according to claim 1with an inorganic or organic acid.
 7. A pharmaceutical compositioncontaining a compound according to claim 1 or a salt with an inorganicor organic acid optionally together with one or more inert carriersand/or diluents.
 8. A process for preparing a composition according toclaim 7, said method comprising incorporating one or more inert carriersand/or diluents by a non-chemical method.
 9. A method of treating adisease selected from the group consisting of type I and type IIdiabetes mellitus, arthritis, obesity, allograft transplantation andosteoporosis caused by calcitonin comprising the step of administeringto a patient in need thereof a pharmaceutically acceptable amount of acompound according to claim 1 or a salt with organic or inorganic acid.10. A process for preparing the compound of formula I according toclaims 1 comprising the steps of deprotecting a compound of generalformula

wherein R¹, R², Y and R³ are as hereinbefore defined and R⁴″ denotes oneof the groups mentioned for R⁴ hereinbefore which contain an imino,amino or alkylamino group, where said imino, amino or alkylamino groupis substituted by a protective group, and subsequently, optionallycleaving said protective group used during the reactions and/oroptionally resolving said compound into its stereoisomers and/orconverting said compound thus obtained into its physiologicallyacceptable salts thereof with an inorganic or organic acid.